Repeat instability: mechanisms of dynamic mutations

Pearson, Christopher E.; Edamura, Kerrie Nichol; Cleary, John D.

doi:10.1038/nrg1689

Cited by 927Genetic Neurodegenerative DiseasesGenetic factors in colorectal cancerDNA Repair Mechanisms

Repeat instability: mechanisms of dynamic mutations

Pearson, Christopher E., Edamura, Kerrie Nichol, Cleary, John D.·2005·Nature Reviews Genetics

DOI 10.1038/nrg1689

Open this paper in CoChat — free account

Abstract

Disease-causing repeat instability is an important and unique form of mutation that is linked to more than 40 neurological, neurodegenerative and neuromuscular disorders. DNA repeat expansion mutations are dynamic and ongoing within tissues and across generations. The patterns of inherited and tissue-specific instability are determined by both gene-specific cis-elements and trans-acting DNA metabolic proteins. Repeat instability probably involves the formation of unusual DNA structures during DNA replication, repair and recombination. Experimental advances towards explaining the mechanisms of repeat instability have broadened our understanding of this mutational process. They have revealed surprising ways in which metabolic pathways can drive or protect from repeat instability.

Integrity signals

Registry

Crossref · 10.1038/nrg1689

Cites

155 of 155 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

A small number of specific normal-length STRs undergo somatic or germline expansion and transition to intermediate, pre-mutation, and mutation repeat unit tract lengths.
“By a process that is poorly understood, a small number of specific normal-length STRs undergo somatic or germline expansion and transition to intermediate, pre-mutation, and mutation (affected) repeat unit tract lengths (Mirkin, 2007; Pearson et al., 2005).”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Pearson et al., 2005
A large number of daSTRs known to undergo paternal instability co-localized to boundaries in mouse sperm and not in mouse oocytes.
“Notably, a large number of daSTRs known to undergo paternal instability (McMurray, 2010; Pearson et al., 2005) co-localized to boundaries in mouse sperm and not in mouse oocytes (Du et al., 2017), suggesting that daSTRs could be at boundaries when germ line expansion takes place (Figure S3).”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Pearson et al., 2005

Comparative aspects of the brain growth spurt
Dobbing, J., & Sands, J. (1979) · Early Human Development · doi:10.1016/0378-3782(79)90022-7 · Cited by 2,506 · see citing works
The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function
Chamberlain, N. L., Driver, E. D., & Miesfeld, R. L. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.15.3181 · Cited by 1,149 · see citing works
Recommendations for a nomenclature system for human gene mutations
Antonarakis, S. E., & Nomenclature Working Group (1998) · Human Mutation · doi:10.1002/(sici)1098-1004(1998)11:1 · Cited by 934 · see citing works
DNA methylation represses <i>FMR-1</i> transcription in fragile X syndrome
Sutcliffe, J. S., Nelson, D. L., Zhang, F., Pieretti, M., Caskey, C. T., Saxe, D., & Warren, S. T. (1992) · Human Molecular Genetics · doi:10.1093/hmg/1.6.397 · Cited by 680 · see citing works
Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain
Curtis, M. A., Penney, E. B., Pearson, A. G., van Roon‐Mom, W., Butterworth, N. J., Dragunow, M., Connor, B. J., & Faull, R. L. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1532244100 · Cited by 522 · see citing works
Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice
MANLEY, K. M., Shirley, T. L., Flaherty, L. A., & Messer, A. C. (1999) · Nature Genetics · doi:10.1038/70598 · Cited by 415 · see citing works
Expansion and Length-Dependent Fragility of CTG Repeats in Yeast
Freudenreich, C. H., Kantrow, S. M., & Zakian, V. A. (1998) · Science · doi:10.1126/science.279.5352.853 · Cited by 403 · see citing works
Mismatch repair and DNA damage signalling
Stojic, L., Brun, R., & Jiricny, J. (2004) · DNA Repair · doi:10.1016/j.dnarep.2004.06.006 · Cited by 396 · see citing works
Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis
Kennedy, L. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg352 · Cited by 384 · see citing works
Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1
Lin, X., Antalffy, B., Kang, D., Orr, H. T., & Zoghbi, H. Y. (2000) · Nature Neuroscience · doi:10.1038/72101 · Cited by 374 · see citing works
Reduced transcriptional regulatory competence of the androgen receptor in X–linked spinal and bulbar muscular atrophy
Mhatre, A. N., Trifiro, M. A., Kaufman, M., Kazemi‐Esfarjani, P., Figlewicz, D. A., Rouleau, G. A., & Pinsky, L. (1993) · Nature Genetics · doi:10.1038/ng1093-184 · Cited by 357 · see citing works
Trinucleotide repeats affect DNA replication in vivo
Samadashwily, G., Raca, G., & Mirkin, S. (1997) · Nature Genetics · doi:10.1038/ng1197-298 · Cited by 343 · see citing works
CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus
Filippova, G. N., Thienes, C. P., Penn, B. H., Cho, D. H., Hu, Y. J., Moore, J. M., Klesert, T. R., Lobanenkov, V. V., & Tapscott, S. J. (2001) · Nature Genetics · doi:10.1038/ng570 · Cited by 332 · see citing works
Somatic mosaicism, germline expansions, germline reversions and intergenerational reductions in myotonic dystrophy males: small pool PCR analyses
Monckton, D. G., Wong, L. J., Ashizawa, T., & Caskey, C. T. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.1.1 · Cited by 326 · see citing works
Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation
Mangiarini, L., Sathasivam, K., Mahal, A., Mott, R., Seller, M. J., & Bates, G. P. (1997) · Nature Genetics · doi:10.1038/ng0297-197 · Cited by 318 · see citing works
Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins.
van den Broek, W. J., Nelen, M., Wansink, D. G., Coerwinkel, M., Riele, H. T., Groenen, P., & Wieringa, B. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.2.191 · Cited by 309 · see citing works
Trinucleotide expansion in haploid germ cells by gap repair
Kovtun, I. V., & McMurray, C. T. (2001) · Nature Genetics · doi:10.1038/86906 · Cited by 276 · see citing works
Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in leukocytes
Thornton, C. A., Johnson, K. J., & Moxley, R. T. (1994) · Annals of Neurology · doi:10.1002/ana.410350116 · Cited by 274 · see citing works
Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines
Beilin, J., Ball, E., Favaloro, J., & Zajac, J. D. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0250085 · Cited by 265 · see citing works
Extreme Heterogeneity in the Molecular Events Leading to the Establishment of Chiasmata during Meiosis I in Human Oocytes
Lenzi, M. L., Smith, J., Snowden, T., Kim, M. S., Fishel, R. A., Poulos, B. K., & Cohen, P. E. (2004) · The American Journal of Human Genetics · doi:10.1086/427268 · Cited by 236 · see citing works
Preferential Nucleosome Assembly at DNA Triplet Repeats from the Myotonic Dystrophy Gene
Wang, Y.-H., Amirhaeri, S., Kang, S., Wells, R. D., & Griffith, J. D. (1994) · Science · doi:10.1126/science.8036515 · Cited by 236 · see citing works
Mismatch repair gene Msh2 modifies the timing of early disease in HdhQ111 striatum
Wheeler, V. C. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg056 · Cited by 232 · see citing works
DNA repair in terminally differentiated cells
Nouspikel, T. (2002) · DNA repair · doi:10.1016/s1568-7864(01)00005-2 · Cited by 226 · see citing works
Expansions and Contractions in a Tandem Repeat Induced by Double-Strand Break Repair
Pâques, F., Leung, W.-Y., & Haber, J. E. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.2045 · Cited by 226 · see citing works
(CAG)n-hairpin DNA binds to Msh2–Msh3 and changes properties of mismatch recognition
Owen, B. A. L., Yang, Z., Lai, M., Gajek, M., Badger, J. D., Hayes, J. J., Edelmann, W., Kucherlapati, R., Wilson, T., & McMurray, C. T. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb965 · Cited by 222 · see citing works
Alanine tracts: the expanding story of human illness and trinucleotide repeats
Brown, L. (2003) · Trends in Genetics · doi:10.1016/j.tig.2003.11.002 · Cited by 218 · see citing works
CTG repeat instability and size variation timing in DNA repair‐deficient mice
Savouret, C., Brisson, E., Essers, J., Kanaar, R., Pastink, A., Riele, H. T., Junien, C., & Gourdon, G. (2003) · EMBO Journal · doi:10.1093/emboj/cdg202 · Cited by 215 · see citing works
Triplet repeats form secondary structures that escape DNA repair in yeast
Moore, H., Greenwell, P. W., Liu, C.-P., Arnheim, N., & Petes, T. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1504 · Cited by 211 · see citing works
Efficient Processing of DNA Ends during Yeast Nonhomologous End Joining
Wilson, T. E., & Lieber, M. R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23599 · Cited by 211 · see citing works
Huntington's disease: a synaptopathy?
Li, J., Plomann, M., & Brundin, P. (2003) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2003.08.006 · Cited by 208 · see citing works
Replication Stalling at Friedreich's Ataxia (GAA)n Repeats In Vivo
Krasilnikova, M. M., & Mirkin, S. M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.6.2286-2295.2004 · Cited by 207 · see citing works
Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells
Cleary, J., Nichol, K., Wang, Y.-H., & Pearson, C. E. (2002) · Nature Genetics · doi:10.1038/ng870 · Cited by 206 · see citing works
Molecular analysis of juvenile Huntington disease: the major influence on (CAG) n repeat length is the sex of the affected parent
Telenius, H., Kremer, H., Thellmann, J., Andrew, S. E., Almqvist, E. W., Anvret, M., Greenberg, C. R., Greenberg, J., Lucotte, G., Squltierl, F., et al. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.10.1535 · Cited by 203 · see citing works
Pms2 is a genetic enhancer of trinucleotide CAG{middle dot}CTG repeat somatic mosaicism: implications for the mechanism of triplet repeat expansion
Gomes-Pereira, M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh186 · Cited by 201 · see citing works
Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease?
Kennedy, L. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.17.2539 · Cited by 199 · see citing works
Characterization of the full fragile X syndrome mutation in fetal gametes
Malter, H. E., Iber, J. C., Willemsen, R., Graaff, E. D., Tarleton, J. C., Leisti, J., Warren, S. T., & Oostra, B. A. (1997) · Nature Genetics · doi:10.1038/ng0297-165 · Cited by 197 · see citing works
An Msh2 Point Mutation Uncouples DNA Mismatch Repair and Apoptosis
Lin, D. P., Wang, Y., Scherer, S. J., Clark, A. B., Yang, K., Avdievich, E., Jin, B., Werling, U., Parris, T., Kurihara, N., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2957 · Cited by 195 · see citing works
Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.
Otten, A. D., & Tapscott, S. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5465 · Cited by 190 · see citing works
Generalized brain and skin proteasome inhibition in Huntington’s disease
Seo, H., Sonntag, K., & Isacson, O. (2004) · Annals of Neurology · doi:10.1002/ana.20207 · Cited by 188 · see citing works
Gametic and somatic tissue–specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1
Chong, S. S., McCall, A. E., Cota, J., Subramony, S. H., Orr, H. T., Hughes, M. R., & Zoghbi, H. Y. (1995) · Nature Genetics · doi:10.1038/ng0795-344 · Cited by 187 · see citing works
Pausing of DNA Synthesis in Vitro at Specific Loci in CTG and CGG Triplet Repeats from Human Hereditary Disease Genes
Kang, S., Ohshima, K., Shimizu, M., Amirhaeri, S., & Wells, R. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.27014 · Cited by 184 · see citing works
Expansions of CAG Repeat Tracts are Frequent in a Yeast Mutant Defective in Okazaki Fragment Maturation
Schweitzer, J. K., & Livingston, D. M. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.1.69 · Cited by 180 · see citing works
Orientation-dependent and sequence-specific expansions of CTG/CAG trinucleotide repeats in Saccharomyces cerevisiae
Miret, J. J., Pessoa-Brandão, L., & Lahue, R. S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12438 · Cited by 178 · see citing works
Inhibition of FEN-1 Processing by DNA Secondary Structure at Trinucleotide Repeats
Spiro, C., Pelletier, R., Rolfsmeier, M. L., Dixon, M. J., Lahue, R. S., Gupta, G., Park, M. S., Chen, X., Mariappan, S. V. S., & McMurray, C. T. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80236-1 · Cited by 177 · see citing works
De Novo Facioscapulohumeral Muscular Dystrophy: Frequent Somatic Mosaicism, Sex-Dependent Phenotype, and the Role of Mitotic Transchromosomal Repeat Interaction between Chromosomes 4 and 10
van der Maarel, S. M., Deidda, G., Lemmers, R. J. L. F., van Overveld, P. G. M., van der Wielen, M. J. R., Hewitt, J., Sandkuijl, L. A., Bakker, E., van Ommen, G. B., Padberg, G. W., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/302730 · Cited by 172 · see citing works
Transgenic mice carrying large human genomic sequences with expanded CTG repeat mimic closely the DM CTG repeat intergenerational and somatic instability
Seznec, H. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.8.1185 · Cited by 165 · see citing works
Replication and Expansion of Trinucleotide Repeats in Yeast
Pelletier, R., Krasilnikova, M. M., Samadashwily, G. M., Lahue, R. S., & Mirkin, S. M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.4.1349-1357.2003 · Cited by 164 · see citing works
Interruptions in the Triplet Repeats of SCA1 and FRAXA Reduce the Propensity and Complexity of Slipped Strand DNA (S-DNA) Formation
Pearson, C. E., Eichler, E. E., Lorenzetti, D., Kramer, S. F., Zoghbi, H. Y., Nelson, D. L., & Sinden, R. R. (1998) · Biochemistry · doi:10.1021/bi972546c · Cited by 159 · see citing works
Slipped (CTG)•(CAG) repeats can be correctly repaired, escape repair or undergo error-prone repair
Panigrahi, G., Lau, R., Montgomery, S., Leonard, M. R., & Pearson, C. E. (2005) · Nature Structural &Molecular Biology · doi:10.1038/nsmb959 · Cited by 159 · see citing works
Analysis of full fragile X mutations in fetal tissues and monozygotic twins indicate that abnormal methylation and somatic heterogeneity are established early in development
Devys, D., Biancalana, V., Rousseau, F., Boué, J., Mandel, J., & Oberlé, I. (1992) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320430134 · Cited by 157 · see citing works
Biochemical Analysis of the DNA Unwinding and Strand Annealing Activities Catalyzed by Human RECQ1*[boxs]
Sharma, S., Sommers, J. A., Choudhary, S., Faulkner, J. K., Cui, S., Andreoli, L., Muzzolini, L., Vindigni, A., & Brosh, R. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500264200 · Cited by 156 · see citing works
Mismatch repair in Escherichia coli enhances instability of (CTG)n triplet repeats from human hereditary diseases.
Jaworski, A., Rosche, W. A., Gellibolian, R., Kang, S.-J., Shimizu, M., Bowater, R. P., Sinden, R. R., & Wells, R. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11019 · Cited by 156 · see citing works
Progression of somatic CTG repeat length heterogeneity in the blood cells of myotonic dystrophy patients
Martorell, L. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.2.307 · Cited by 156 · see citing works
YB-1 promotes strand separation in vitro of duplex DNA containing either mispaired bases or cisplatin modifications, exhibits endonucleolytic activities and binds several DNA repair proteins
Gaudreault, I. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh170 · Cited by 154 · see citing works
Alterations of androgen receptor in prostate cancer
Linja, M. J., & Visakorpi, T. (2004) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2004.10.012 · Cited by 151 · see citing works
The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA
Cheok, C. F. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki712 · Cited by 147 · see citing works
Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases
Pearson, C. E. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.7.1117 · Cited by 144 · see citing works
Hypermutable myotonic dystrophy CTG repeats in transgenic mice
Monckton, D., Coolbaugh, M. I., Ashizawa, K. T., Siciliano, M., & Caskey, C. (1997) · Nature Genetics · doi:10.1038/ng0297-193 · Cited by 142 · see citing works
Dramatic, expansion-biased, age-dependent, tissue-specific somatic mosaicism in a transgenic mouse model of triplet repeat instability
Fortune, M. T. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.3.439 · Cited by 141 · see citing works
The contribution of cis-elements to disease-associated repeat instability: clinical and experimental evidence
Cleary, J. D., & Pearson, C. E. (2003) · Cytogenetic and Genome Research · doi:10.1159/000072837 · Cited by 138 · see citing works
Recombination‐induced CAG trinucleotide repeat expansions in yeast involve the MRE11–RAD50–XRS2 complex
Richard, G., Goellner, G. M., McMurray, C. T., & Haber, J. E. (2000) · The EMBO Journal · doi:10.1093/emboj/19.10.2381 · Cited by 135 · see citing works
Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice
Gourdon, G., Radvanyi, F., Lia, A., Duros, C., Blanche, M., Abitbol, M. M., Junien, C., & Hofmann-Radvanyi, H. (1997) · Nature Genetics · doi:10.1038/ng0297-190 · Cited by 128 · see citing works
Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients.
Sato, T., Oyake, M., Nakamura, K., Nakao, K., Fukusima, Y., Onodera, O., Igarashi, S., Takano, H., Kikugawa, K., Ishida, Y., et al. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.1.99 · Cited by 125 · see citing works
Genetic Instabilities in (CTG·CAG) Repeats Occur by Recombination
Jakupciak, J. P., & Wells, R. D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23468 · Cited by 123 · see citing works
Cis-acting modifiers of expanded CAG/CTG triplet repeat expandability: associations with flanking GC content and proximity to CpG islands
Brock, G. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.6.1061 · Cited by 122 · see citing works
Reduction in Size of the Myotonic Dystrophy Trinucleotide Repeat Mutation During Transmission
O'Hoy, K., Tsilfidis, C., Mahadevan, M. S., Neville, C., Barceló, J. M., Hunter, A. G. W., & Korneluk, R. G. (1993) · Science · doi:10.1126/science.8094260 · Cited by 117 · see citing works
Timing of the absence of FMR1 expression in full mutation chorionic villi
Willemsen, R., Bontekoe, C. J. M., Severijnen, L.-A. W. F. M., & Oostra, B. A. (2002) · Human Genetics · doi:10.1007/s00439-002-0723-5 · Cited by 114 · see citing works
Transgenic mice with an expanded CAG repeat controlled by the human AR promoter show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death
Adachi, H. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.10.1039 · Cited by 112 · see citing works
Meiotic instability of CAG repeat tracts occurs by double-strand break repair in yeast
Jankowski, C., Nasar, F., & Nag, D. K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040460297 · Cited by 110 · see citing works
SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence changes may play a role in reduced penetrance
Moseley, M. L. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.14.2125 · Cited by 109 · see citing works
Inhibition of Flap Endonuclease 1 by Flap Secondary Structure and Relevance to Repeat Sequence Expansion
Henricksen, L. A., Tom, S., Liu, Y., & Bambara, R. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909635199 · Cited by 107 · see citing works
Increased trinucleotide repeat instability with advanced maternal age.
Kaytor, M., Burright, E., Duvick, L., Zoghbi, H., & Orr, H. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.12.2135 · Cited by 106 · see citing works
MSH2-Dependent Germinal CTG Repeat Expansions Are Produced Continuously in Spermatogonia from DM1 Transgenic Mice
Savouret, C., Cordier, C., Megret, J., Riele, H. T., Junien, C., & Gourdon, G. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.24.2.629-637.2004 · Cited by 105 · see citing works
Huntington disease expansion mutations in humans can occur before meiosis is completed
Yoon, S., Dubeau, L., de Young, M., Wexler, N. S., & Arnheim, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1331390100 · Cited by 104 · see citing works
On the Roles of Saccharomyces cerevisiae Dna2p and Flap Endonuclease 1 in Okazaki Fragment Processing
Kao, H.-I., Veeraraghavan, J., Polaczek, P., Campbell, J. L., & Bambara, R. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313216200 · Cited by 102 · see citing works
Unusual mutations in high functioning fragile X males: apparent instability of expanded unmethylated CGG repeats.
Wöhrle, D., Salat, U., Gläser, D., Mücke, J., Meisel-Stosiek, M., Schindler, D., Vogel, W., & Steinbach, P. J. (1998) · Journal of Medical Genetics · doi:10.1136/jmg.35.2.103 · Cited by 100 · see citing works
Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients
Sathasivam, K. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.21.2425 · Cited by 100 · see citing works
GAA repeat instability in Friedreich ataxia YAC transgenic mice
Al‐Mahdawi, S., Pinto, R. M., Ruddle, P., Carroll, C. J., Webster, Z., & Pook, M. A. (2004) · Genomics · doi:10.1016/j.ygeno.2004.04.003 · Cited by 99 · see citing works
Mutations in Yeast Replication Proteins That Increase CAG/CTG Expansions Also Increase Repeat Fragility
Callahan, J. L., Andrews, K. J., Zakian, V. A., & Freudenreich, C. H. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7849-7860.2003 · Cited by 99 · see citing works
Somatic instability of the CTG repeat in mice transgenic for the myotonic dystrophy region is age dependent but not correlated to the relative intertissue transcription levels and proliferative capacities.
Lia, A., Seznec, H., Hofmann-Radvanyi, H., Radvanyi, F., Duros, C., Saquet, C., Blanche, M., Junien, C., & Gourdon, G. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.8.1285 · Cited by 94 · see citing works
Destabilization of CAG Trinucleotide Repeat Tracts by Mismatch Repair Mutations in Yeast
Schweitzer, J. K., & Livingston, D. M. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.3.349 · Cited by 93 · see citing works
Replication fork dynamics and dynamic mutations: the fork-shift model of repeat instability.
Cleary, J., & Pearson, C. E. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.03.008 · Cited by 92 · see citing works
Transcription increases the deletion frequency of long CTG.CAG triplet repeats from plasmids in Escherichia coli
Bowater, R. P. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.14.2861 · Cited by 92 · see citing works
Heterogeneity of DM kinase repeat expansion in different fetal tissues and further expansion during cell proliferation in vitro: evidence for a causal involvement of methyl-directed DNA mismatch repair in triplet repeat stability
Wohrle, D., Kennerknecht, I., Wolf, M., Enders, H., Schwemmle, S., & Steinbach, P. J. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.7.1147 · Cited by 90 · see citing works
RECQ1 Helicase Interacts with Human Mismatch Repair Factors That Regulate Genetic Recombination*[boxs]
Doherty, K. M., Sharma, S., Uzdilla, L. A., Wilson, T., Cui, S., Vindigni, A., & Brosh, R. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500265200 · Cited by 88 · see citing works
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability
Spada, A. R. L. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.6.959 · Cited by 88 · see citing works
Somatic mosaicism for Friedreich's ataxia GAA triplet repeat expansions in the central nervous system
Montermini, L., Kish, S. J., Jiralerspong, S., Lamarche, J. B., & Pandolfo, M. (1997) · Neurology · doi:10.1212/wnl.49.2.606 · Cited by 86 · see citing works
Analysis of the CTG repeat in skeletal muscle of young and adult myotonic dystrophy patients: when does the expansion occur?
Zatz, M., Passos-Bueno, M., Cerqueira, A., Marie, S. K., Vainzof, M., & Pavanello, R. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.3.401 · Cited by 86 · see citing works
Nucleotide excision repair affects the stability of long transcribed (CTG*CAG) tracts in an orientation-dependent manner in Escherichia coli
Parniewski, P., Bacolla, A., Jaworski, A., & Wells, R. D. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.2.616 · Cited by 86 · see citing works
Replication Inhibitors Modulate Instability of an Expanded Trinucleotide Repeat at the Myotonic Dystrophy Type 1 Disease Locus in Human Cells
Yang, Z., Lau, R., Marcadier, J. L., Chitayat, D. A., & Pearson, C. E. (2003) · The American Journal of Human Genetics · doi:10.1086/379523 · Cited by 86 · see citing works
Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral-pallidoluysian atrophy: cellular population-dependent dynamics of mitotic instability.
Takano, H., Onodera, O., Takahashi, H., Igarashi, S., Yamada, M., Oyake, M., Ikeuchi, T., Koide, R., Tanaka, H., Iwabuchi, K., et al. (1996) · PubMed Central · Cited by 84 · see citing works
Genome-wide demethylation destabilizes CTG·CAG trinucleotide repeats in mammalian cells
Gorbunova, V. A., Seluanov, A., Mittelman, D., & Wilson, J. H. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh317 · Cited by 84 · see citing works
Base Stacking and Even/Odd Behavior of Hairpin Loops in DNA Triplet Repeat Slippage and Expansion with DNA Polymerase
Hartenstine, M. J., Goodman, M. F., & Petruska, J. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.24.18382 · Cited by 83 · see citing works
Mouse tissue culture models of unstable triplet repeats: in vitro selection for larger alleles, mutational expansion bias and tissue specificity, but no association with cell division rates.
Gomes-Pereira, M., Fortune, M. T., & Monckton, D. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.8.845 · Cited by 83 · see citing works
The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase
Yang, Q., Zhang, R., Wang, X. W., Linke, S. P., Sengupta, S., Hickson, I. D., Pedrazzi, G., Perrera, C., Štagljar, I., Littman, S. J., et al. (2004) · Oncogene · doi:10.1038/sj.onc.1207462 · Cited by 80 · see citing works
Slipping while sleeping? Trinucleotide repeat expansions in germ cells
Pearson, C. E. (2003) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2003.09.006 · Cited by 79 · see citing works
Intergenerational Instability of the Expanded CTG Repeat in the DMPK Gene: Studies in Human Gametes and Preimplantation Embryos
Temmerman, N. D., Sermon, K., Seneca, S., Rycke, M. D., Hilven, P., Lissens, W., Steirteghem, A. V., & Liebaers, I. (2004) · The American Journal of Human Genetics · doi:10.1086/422762 · Cited by 79 · see citing works
Nuclease-Deficient FEN-1 Blocks Rad51/BRCA1-Mediated Repair and Causes Trinucleotide Repeat Instability
Spiro, C., & McMurray, C. T. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.17.6063-6074.2003 · Cited by 78 · see citing works
Parental gender, age at birth and expansion length influence GAA repeat intergenerational instability in the X25 gene: pedigree studies and analysis of sperm from patients with Friedreich's Ataxia
Michele, G. D., Cavalcanti, F., Criscuolo, C., Pianese, L., Monticelli, A., Filla, A., & Cocozza, S. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.12.1901 · Cited by 76 · see citing works
Saccharomyces cerevisiae Flap Endonuclease 1 Uses Flap Equilibration To Maintain Triplet Repeat Stability
Liu, Y., Zhang, H., Veeraraghavan, J., Bambara, R. A., & Freudenreich, C. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.9.4049-4064.2004 · Cited by 76 · see citing works
Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice
Libby, R. T. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg006 · Cited by 75 · see citing works
Somatic Instability of the Myotonic Dystrophy (CTG)n Repeat during Human Fetal Development
Martorell, L., Johnson, K. J., Boucher, C. A., & Baiget, M. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.6.877 · Cited by 75 · see citing works
DNA repair during organogenesis
Vinson, R. K., & Hales, B. F. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(02)00223-3 · Cited by 71 · see citing works
Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic
Moutou, C. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.7.971 · Cited by 70 · see citing works
Tissue-Specific Somatic Mosaicism in Spinal and Bulbar Muscular Atrophy Is Dependent on CAG-Repeat Length and Androgen Receptor–Gene Expression Level
Tanaka, F., Reeves, M. F., Ito, Y., Matsumoto, M., Li, M., Miwa, S., Inukai, A., Yamamoto, M., Doyu, M., Yoshida, M., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302578 · Cited by 68 · see citing works
Brain regional differences in the expansion of a CAG repeat in the spinocerebellar ataxias: Dentatorubral‐pallidoluysian atrophy, machado‐joseph disease, and spinocerebellar ataxia type 1
Hashida, H., Goto, J., Kurisaki, H., Mizusawa, H., & Kanazawa, I. (1997) · Annals of Neurology · doi:10.1002/ana.410410414 · Cited by 67 · see citing works
Length of CTG·CAG repeats determines the influence of mismatch repair on genetic instability 1 1Edited by M. Yaniv
Parniewski, P., Jaworski, A., Wells, R. D., & Bowater, R. P. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3796 · Cited by 65 · see citing works
Replication-mediated instability of the GAA triplet repeat mutation in Friedreich ataxia
Pollard, L. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh933 · Cited by 65 · see citing works
Somatic mosaicism in the central nervous system in spinocerebellar ataxia type 1 and machado‐joseph disease
Lopes‐Cendes, Í., Maciel, P., Kish, S. J., Gaspar, C., Silveira, I., Robitaille, Y., Clark, H. B., Koeppen, A. H., NANCE, M. A., Schut, L. J., et al. (1996) · Annals of Neurology · doi:10.1002/ana.410400211 · Cited by 63 · see citing works
Progressive atrophy of cerebellum and brainstem as a function of age and the size of the expanded CAG repeats in the MJD1 gene in Machado‐Joseph disease
Onodera, O., Idezuka, J., Igarashi, S., Takiyama, Y., Endo, K., Takano, H., Oyake, M., Tanaka, H., Inuzuka, T., Hayashi, T., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410430305 · Cited by 62 · see citing works
CpG Methylation Modifies the Genetic Stability of Cloned Repeat SequencesPreprint
Nichol, K., & Pearson, A. C. E. (2002) · Genome Research · doi:10.1101/gr.74502 · Cited by 62 · see citing works
Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1
Watase, K. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg300 · Cited by 61 · see citing works
Different mechanisms underlie DNA instability in Huntington disease and colorectal cancer.
Goellner, G. M., Tester, D. J., Thibodeau, S. N., Almqvist, E. W., Goldberg, Y. P., Hayden, M. R., & McMurray, C. T. (1997) · PubMed · Cited by 61 · see citing works
The Impact of Lagging Strand Replication Mutations on the Stability of CAG Repeat Tracts in Yeast
Ireland, M. J., Reinke, S. S., & Livingston, D. M. (2000) · Genetics · doi:10.1093/genetics/155.4.1657 · Cited by 60 · see citing works
Chemotherapeutic deletion of CTG repeats in lymphoblast cells from DM1 patients
Hashem, V. I. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh976 · Cited by 60 · see citing works
Mechanism and Timing of Mitotic Rearrangements in the Subtelomeric D4Z4 Repeat Involved in Facioscapulohumeral Muscular Dystrophy
Lemmers, R. J. L. F., van Overveld, P. G. M., Sandkuijl, L. A., Vrieling, H., Padberg, G. W., Frants, R. R., & van der Maarel, S. M. (2004) · The American Journal of Human Genetics · doi:10.1086/422175 · Cited by 58 · see citing works
Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period.
Martorell, L., Martínez, J. M., Carey, N., Johnson, K. J., & Baiget, M. (1995) · Journal of Medical Genetics · doi:10.1136/jmg.32.8.593 · Cited by 56 · see citing works
Involvement of the Nucleotide Excision Repair Protein UvrA in Instability of CAG·CTG Repeat Sequences in Escherichia coli *
Oussatcheva, E. A., Hashem, V., Zou, Y., Sinden, R., & Potaman, V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104697200 · Cited by 55 · see citing works
Role of Replication and CpG Methylation in Fragile X Syndrome CGG Deletions in Primate Cells
Edamura, K. N., Leonard, M. R., & Pearson, C. E. (2005) · The American Journal of Human Genetics · doi:10.1086/427928 · Cited by 52 · see citing works
Human Bloom Protein Stimulates Flap Endonuclease 1 Activity by Resolving DNA Secondary Structure
Wang, W., & Bambara, R. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412359200 · Cited by 51 · see citing works
Allele diversity and germline mutation at the insulin minisatellite
Stead, J. D. H. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.5.713 · Cited by 51 · see citing works
Long CTG Tracts from the Myotonic Dystrophy Gene Induce Deletions and Rearrangements during Recombination at the APRT Locus in CHO Cells
Meservy, J. L., Sargent, R. G., Iyer, R. R., Chan, F., McKenzie, G. J., Wells, R. D., & Wilson, J. H. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.9.3152-3162.2003 · Cited by 50 · see citing works
Structure-Forming CAG/CTG Repeat Sequences are Sensitive to Breakage in the Absence of Mrc1 Checkpoint Function and S-Phase Checkpoint Signaling: Implications for Trinucleotide Repeat Expansion Diseases
Freudenreich, C. H., & Lahiri, M. (2004) · Cell Cycle · doi:10.4161/cc.3.11.1246 · Cited by 48 · see citing works
Loss of mutation at the FMR1 locus through multiple exchanges between maternal X chromosomes
van den Ouweland, A. M. W., Deelen, W. H., Kunst, C. B., Uzielli, M. L. G., Nelson, D. L., Warren, S. T., Oostra, B. A., & Halley, D. J. J. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.10.1823 · Cited by 46 · see citing works
Single cell analysis of CAG repeat in brains of dentatorubral-pallidoluysian atrophy (DRPLA)
Hashida, H., Goto, J., Suzuki, T., Jeong, S.-Y., Masuda, N., Ooie, T., Tachiiri, Y., Tsuchiya, H., & Kanazawa, I. (2001) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(01)00596-2 · Cited by 46 · see citing works
Two opposing effects of mismatch repair on CTG repeat instability in Escherichia coli
Schmidt, K. H., Abbott, C. M., & Leach, D. R. F. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01727.x · Cited by 44 · see citing works
Stability of triplet repeats of myotonic dystrophy and fragile X loci in human mutator mismatch repair cell lines
Kramer, P. R., Pearson, C. E., & Sinden, R. R. (1996) · Human Genetics · doi:10.1007/s004390050179 · Cited by 43 · see citing works
Skeletal muscle recovery after tenotomy and 7-day delayed muscle length restoration
Abrams, R. A., Tsai, A. M., Watson, B., Jamali, A. A., & Lieber, R. L. (2000) · Muscle & Nerve · doi:10.1002/(sici)1097-4598(200005)23:5 · Cited by 39 · see citing works
hMutSalpha forms an ATP-dependent complex with hMutLalpha and hMutLbeta on DNA
Plotz, G. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.3.711 · Cited by 39 · see citing works
Differential somatic CAG repeat instability in variable brain cell lineage in dentatorubral pallidoluysian atrophy (DRPLA): a laser-captured microdissection (LCM)-based analysis
Watanabe, H., Tanaka, F., Doyu, M., Riku, S., Yoshida, M., Hashizume, Y., & Sobue, G. (2000) · Human Genetics · doi:10.1007/s004390000400 · Cited by 38 · see citing works
Fidelity of Primate Cell Repair of a Double-strand Break within a (CTG)·(CAG) Tract
Marcadier, J. L., & Pearson, C. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304284200 · Cited by 37 · see citing works
Effect of CAT or AGG Interruptions and CpG Methylation on Nucleosome Assembly upon Trinucleotide Repeats on Spinocerebellar Ataxia, Type 1 and Fragile X Syndrome*
Mulvihill, D. J., Edamura, K. N., Hagerman, K. A., Pearson, C. E., & Wang, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m413239200 · Cited by 36 · see citing works
The ‘flap’ endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease
Otto, C., Almqvist, E. W., Hayden, M. R., & Andrew, S. (2001) · Clinical Genetics · doi:10.1034/j.1399-0004.2001.590210.x · Cited by 35 · see citing works
Neuropathological diagnosis and CAG repeat expansion in Huntington's disease.
Xuereb, J. H., MacMillan, J., Snell, R. G., Davies, P., & Harper, P. S. (1996) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.60.1.78 · Cited by 34 · see citing works
Candidate DNA replication initiation regions at human trinucleotide repeat disease loci
Nenguke, T. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg111 · Cited by 34 · see citing works
Fragile X premutations and (TA)n estrogen receptor polymorphism in women with ovarian dysfunction
Syrrou, M., Georgiou, I. A., Patsalis, P. C., Bouba, I., Adonakis, G., & Pagoulatos, G. N. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990528)84:3 · Cited by 33 · see citing works
Fully Expanded FMR1CGG Repeats Exhibit a Length-and Differentiation-Dependent Instability in Cell Hybrids That is Independent of DNA Methylation
Burman, R. W., Popovich, B. W., Jacky, P. B., & Turker, M. S. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.12.2293 · Cited by 33 · see citing works
Genetically confirmed clinical Huntington's disease with no observable cell loss
Caramins, M. C. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.7.968 · Cited by 32 · see citing works
Human FEN-1 can process the 5'-flap DNA of CTG/CAG triplet repeat derived from human genetic diseases by length and sequence dependent manner
Lee, S., & Park, M. S. (2002) · Experimental & Molecular Medicine · doi:10.1038/emm.2002.44 · Cited by 31 · see citing works
Most meiotic CAG repeat tract-length alterations in yeast are SPO11 dependent
Jankowski, C., & Nag, D. K. (2002) · Zeitschrift für Induktive Abstammungs- und Vererbungslehre · doi:10.1007/s00438-001-0635-4 · Cited by 30 · see citing works
Age and insertion site dependence of repeat number instability of a human DM1 transgene in individual mouse sperm
Zhang, Y. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.7.791 · Cited by 30 · see citing works
The expanded CAG repeat associated with juvenile Huntington disease shows a common origin of most or all neurons and glia in human cerebrum
Kahlem, P., & Djian, P. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01029-6 · Cited by 29 · see citing works
DNA Double-strand Breaks Induce Deletion of CTG·CAG Repeats in an Orientation-dependent Manner in Escherichia coli
Hebert, M. L., Spitz, L. A., & Wells, R. D. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.12.038 · Cited by 29 · see citing works
A SCA7 CAG/CTG repeat expansion is stable in Drosophila melanogaster despite modulation of genomic context and gene dosage
Jackson, S. M., Whitworth, A. J., Greene, J. C., Libby, R. T., Baccam, S. L., Pallanck, L. J., & Spada, A. R. L. (2005) · Gene · doi:10.1016/j.gene.2004.12.008 · Cited by 29 · see citing works
An autopsy case with clinically and molecular genetically diagnosed Huntington's disease with only minimal non-specific neuropathological findings.
Mizuno, H., Shibayama, H., Tanaka, F., Doyu, M., Sobue, G., Iwata, H., Kobayashi, H., Yamada, K., Iwai, K., Takeuchi, T., et al. (2000) · PubMed · Cited by 29 · see citing works
Modulation of transcription reveals a new mechanism of triplet repeat instability in Escherichia coli
Schumacher, S. B., Pinet, I., & Bichara, M. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4489 · Cited by 28 · see citing works
In situ shortening of CAG repeat length within the androgen receptor gene in prostatic cancer and its possible precursors
Tsujimoto, Y., Takakuwa, T., Takayama, H., Nishimura, K., Okuyama, Ä., Aozasa, K., & Nonomura, N. (2003) · The Prostate · doi:10.1002/pros.10333 · Cited by 28 · see citing works
Increased Instability of Human CTG Repeat Tracts on Yeast Artificial Chromosomes during Gametogenesis
Cohen, H. Y., Sears, D. D., Zenvirth, D., Hieter, P., & Simchen, G. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4153 · Cited by 28 · see citing works
Increase of FMRP expression, raised levels ofFMR1 mRNA, and clonal selection in proliferating cells with unmethylated fragile X repeat expansions: a clue to the sex bias in the transmission of full mutations?
Salat, U., Bardoni, B., Wöhrle, D., & Steinbach, P. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.11.842 · Cited by 24 · see citing works
Somatic stability in chorionic villi samples and other Huntington fetal tissues
Benitez, J. J., Robledo, M., Ramos, C., Ayuso, C., Astarloa, R., Y�benes, J. G., & Brambati, B. (1995) · Human Genetics · doi:10.1007/bf00207386 · Cited by 21 · see citing works
Larger CAG expansions in skeletal muscle compared with lymphocytes in Kennedy disease but not in Huntington disease
Ansved, T., Lundin, A., & Anvret, M. (1998) · Neurology · doi:10.1212/wnl.51.5.1442 · Cited by 20 · see citing works
A Patient with Myotonic Dystrophy Type 1 (DM1) Accompanied by Laryngeal and Renal Cell Carcinomas Had a Small CTG Triplet Repeat Expansion But No Somatic Instability in Normal Tissues.
Kinoshita, M., Osanai, R., Kikkawa, M., Adachi, A., Ohtake, T., Komori, T., Hashimoto, K., ITOYAMA, S., Mitarai, T., & Hirose, K. (2002) · Internal Medicine · doi:10.2169/internalmedicine.41.312 · Cited by 17 · see citing works
Long‐term potentiation in the hippocampus of fragile X knockout mice
Godfraind, J., Reyniers, E., Boulle, K. D., D’Hooge, R., Deyn, P. P. D., Bakker, C. E., Oostra, B. A., Kooy, R. F., & Willems, P. J. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960809)64:2 · Cited by 16 · see citing works
Neurodegeneration in Xeroderma Pigmentosum: a trinucleotide repeat mutation analysis
Grewal, R. P. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(99)00031-3 · Cited by 9 · see citing works
Spinal and bulbar muscular atrophy (SBMA): Somatic stability of an expanded CAG repeat in fetal tissues
Jedele, K. B., Wahl, D., Chahrokh-Zadeh, S., Wirtz, A., Murken, J. D., & Holinski‐Feder, E. (1998) · Clinical Genetics · doi:10.1111/j.1399-0004.1998.tb03718.x · Cited by 8 · see citing works

Flagged first, then by citations

2 of the 157 references couldn’t be matched to a known paper.

Sorted by citations

Oxidative Stress: A Key Modulator in Neurodegenerative Diseases
Singh, A., Kukreti, R., Saso, L., & Kukreti, S. (2019) · Molecules · doi:10.3390/molecules24081583 · Cited by 2,305 · see citing works
“It has been shown that repairing damaged DNA might lead to the expansion and instability of CAG trinucleotide repeats in mutant Huntingitin [136].”
Background
Circular dichroism and conformational polymorphism of DNA
Kypr, J., Kejnovská, I., Renčiuk, D., & Vorlı́čková, M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp026 · Cited by 1,782 · see citing works
“Poly[d(A)] poly[d(T)] and poly[d(G)] poly[d(C)] adopt unusual B-forms.”
BackgroundInfluential
Mechanisms and functions of DNA mismatch repair
Li, G. (2007) · Cell Research · doi:10.1038/cr.2007.115 · Cited by 1,479 · see citing works
Microsatellite markers: an overview of the recent progress in plants
Kalia, R. K., Manoj, K., Kalia, S., Singh, R., & Dhawan, A. K. (2010) · Euphytica · doi:10.1007/s10681-010-0286-9 · Cited by 1,037 · see citing works
“Microsatellite genesis is an evolutionarily dynamic process and has proven to be exceedingly complex (Ellegren 2004; Pearson et al. 2005).”
Background
R Loops: From Transcription Byproducts to Threats to Genome Stability
Aguilera, A., & García‐Muse, T. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.009 · Cited by 1,029 · see citing works
“Similarly, DNA repeats with the potential to form hairpins are a strong source of DNA breaks and DNA polymerase stalling (reviewed in Aguilera and Gómez-González, 2008; Mirkin and Mirkin, 2007; Pearson et al., 2005).”
Background
Expandable DNA repeats and human disease
Mirkin, S. M. (2007) · Nature · doi:10.1038/nature05977 · Cited by 934 · see citing works
Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics
Patel, D. J., Phan, A. T., & Kuryavyi, V. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm711 · Cited by 879 · see citing works
“A series of nucleotide or repeat expansion disorders caused by the dynamic intergenerational expansion of triple repeat d(CGG)n–d(CCG)n, d(CAG)n–d(CTG)n and d(GAA)n–d(TTC)n sequences are associated with neurological, neuromuscular and neurodegenerative disorders (143,144).”
Background
RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention
Donnelly, C. J., Zhang, P.-W., Pham, J. T., Haeusler, A. R., Mistry, N. A., Vidensky, S., Daley, E. L., Poth, E. M., Hoover, B., Fines, D. M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.015 · Cited by 877 · see citing works
“Since the discovery of pathogenic repeat expansions as a mechanism of disease in the 1990s, the list of neurodegenerative and neuromuscular disorders characterized by unstable repeat expansions has grown to over 20 (Brouwer et al., 2009; Pearson et al., 2005; Todd and Paulson, 2010).”
Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond
Dürr, A. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70183-6 · Cited by 658 · see citing works
Full-Length Human Mutant Huntingtin with a Stable Polyglutamine Repeat Can Elicit Progressive and Selective Neuropathogenesis in BACHD Mice
Gray, M., Shirasaki, D., Cepeda, C., André, V., Wilburn, B., Lu, X.-H., Tao, J., Yamazaki, I., Li, S.-H., Sun, Y. E., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0857-08.2008 · Cited by 616 · see citing works
“Polyglutamine repeats are stable in BACHD mice Both germline and somatic repeat instability is a feature of triplet repeat disorders including HD (Pearson et al., 2005), and has been observed in mouse models of these disorders (Mangiarini et al.”
Background
Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes
Richard, G., Kerrest, A., & Dujon, B. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00011-08 · Cited by 549 · see citing works
Double-Strand Breaks in Heterochromatin Move Outside of a Dynamic HP1a Domain to Complete Recombinational Repair
Chiolo, I., Minoda, A., Colmenares, S. U., Polyzos, A. A., Costes, S. V., & Karpen, G. H. (2011) · Cell · doi:10.1016/j.cell.2011.02.012 · Cited by 516 · see citing works
“Recombination between identical repeats on nonhomologous chromosomes produces dicentric and acentric chromosomes that are known to contribute to human diseases such as cancer and infertility (Pearson et al., 2005).”
Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene
Liu, X. S., Wu, H., Krzisch, M., Wu, X., Graef, J. D., Muffat, J., Hnisz, D., Li, C. H., Yuan, B., Xu, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.012 · Cited by 506 · see citing works
“Trinucleotide repeat expansions play a pathological role in several neurological, neurodegenerative, and neuromuscular disorders such as FXS, Huntington’s disease, spinocerebellar ataxia, and myotonic dystrophy (Nelson et al., 2013; Pearson et al., 2005).”
Background
Heterochromatin: Guardian of the Genome
Janssen, A., Colmenares, S. U., & Karpen, G. H. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062653 · Cited by 500 · see citing works
The myotonic dystrophies: molecular, clinical, and therapeutic challenges
Udd, B., & Krahe, R. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70204-1 · Cited by 493 · see citing works
Repeat expansion disease: progress and puzzles in disease pathogenesis
Spada, A. R. L., & Taylor, J. P. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2748 · Cited by 479 · see citing works
“CTCF has also been implicated in genetic instability, which occurs in most repeat expansion disease”
Background
Replication fork stalling at natural impediments
Mirkin, E. V., & Mirkin, S. M. (2007) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00030-06 · Cited by 482 · see citing works
30 years of repeat expansion disorders: What have we learned and what are the remaining challenges?
Depienne, C., & Mandel, J.-L. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.03.011 · Cited by 429 · see citing works
“However, the observations of expansions and contractions in non-dividing cells have indicated that other mechanisms are at play, and there is increasing evidence from mouse models, and very recently from affected individuals, that somatic stability or instability of repeat expansions largely depends on DNA mismatch re…”
Background
Causes of genome instability
Aguilera, A., & García-Muse, T. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-111212-133232 · Cited by 476 · see citing works
“Depending on the mechanisms involved, genome instability can result in (a) mutations, including point mutations and microsatellite contractions and expansions caused by erroneous or error-prone DNA synthesis, defective nucleotide or base excision repair (NER/BER), or mismatch repair (MMR), (b) variations in chromosome…”
BackgroundInfluential
Repeat instability as the basis for human diseases and as a potential target for therapy
López Castel, A., Cleary, J. D., & Pearson, C. E. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2854 · Cited by 429 · see citing works
“Trinucleotide repeats (TNRs), which include CAG, CTG, CGG and GAA triplets, are the most common unstable disease-associated DNA repeats, but tetranucleotides, pentanucleotides, minisatellites and megasatellites are also involved in causing diseas”
Background
OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells
Kovtun, I. V., Liu, Y., Bjoras, M., Klungland, A., Wilson, S. H., & McMurray, C. T. (2007) · Nature · doi:10.1038/nature05778 · Cited by 433 · see citing works
The Pathophysiology of Fragile X Syndrome
Penagarikano, O., Mulle, J. G., & Warren, S. T. (2007) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.8.080706.092249 · Cited by 420 · see citing works
“Flaps containing repeats could acquire different DNA conformations that enable them to escape FEN-1 cleavage occur; massive expansions could take place by some continuous slippage due to a block in the replication process generated by alternative structures formed by the trinucleotide repeat sequences (89).”
Background
Challenges in analysis and interpretation of microsatellite data for population genetic studies
Putman, A. I., & Carbone, I. (2014) · Ecology and Evolution · doi:10.1002/ece3.1305 · Cited by 412 · see citing works
“…2013), for their reported influence as functional elements (Haasl and Payseur 2013; Sawaya et al. 2013) such as their importance in human diseases (Pearson et al. 2005; Brouwer et al. 2009), in taxa that are slowly evolving or highly clonal, or to study genome evolution (Stolle et al. 2013) or…”
Background
Differential modeling of Fragile X syndrome by human embryonic stem cells and induced-pluripotent stem cells
Urbach, A., Bar-Nur, O., Daley, G., & Benvenisty, N. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.04.005 · Cited by 411 · see citing works
“The vast majority of FX patients do not express FMR1 resulting from CGG triplet repeat expansion in the 50 untranslated region of the gene (Pearson et al., 2005; Verkerk et al., 1991).”
Background
Non-B DNA structure-induced genetic instability and evolution
Zhao, J., Bacolla, A., Wang, G., & Vásquez, K. M. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0131-2 · Cited by 405 · see citing works
“Studies using model systems suggest that instability caused by trinucleotide repeats and other non-B DNA-forming sequences may occur via aberrant DNA replication events [16, 113, 114], as well as replication-independent mechanisms in non-proliferating tissues [115].”
Myotonic Dystrophy
Thornton, C. A. (2014) · Neurologic Clinics · doi:10.1016/j.ncl.2014.04.011 · Cited by 382 · see citing works
Circular Dichroism Spectroscopy of DNA: From Duplexes to Quadruplexes
Vorlı́čková, M., Kejnovská, I., Bednářová, K., Renčiuk, D., & Kypr, J. (2012) · Chirality · doi:10.1002/chir.22064 · Cited by 341 · see citing works
Chromatin and nucleosome dynamics in DNA damage and repairPreprint
Hauer, M., & Gasser, S. M. (2017) · Genes & Development · doi:10.1101/gad.307702.117 · Cited by 320 · see citing works
“Illegitimate recombination events in heterochromatin can result in translocations, duplications, and deletions, reminiscent of the alterations found in human pathologies (Pearson et al. 2005).”
Background
lobSTR: A short tandem repeat profiler for personal genomesPreprint
Gymrek, M., Golan, D., Rosset, S., & Erlich, Y. (2012) · Genome Research · doi:10.1101/gr.135780.111 · Cited by 327 · see citing works
“STR expansions are implicated in the etiology of a variety of genetic disorders, such as Huntingon’s Disease and Fragile-X Syndrome (Pearson et al. 2005; Mirkin 2007).”
Background
The landscape of human STR variation
Willems, T., Gymrek, M., Highnam, G., The 1000 Genomes Project Consortium, Mittelman, D., & Erlich, Y. (2014) · Genome Research · doi:10.1101/gr.177774.114 · Cited by 283 · see citing works
The Disease-associated r(GGGGCC) Repeat from the C9orf72 Gene Forms Tract Length-dependent Uni- and Multimolecular RNA G-quadruplex Structures
Reddy, K., Zamiri, B., Stanley, S. Y., Macgregor, R. B., & Pearson, C. E. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.452532 · Cited by 314 · see citing works
“This suggested that ALS-FTDmay share a toxic RNA pathogenic path with myotonic dystrophy whose r(CUG)n repeatcontaining RNA sequesters MBNL1 proteins bound to the expanded repeat.”
BackgroundInfluential
Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells
Holkers, M., Maggio, I., Liu, J., Janssen, J. M., Miselli, F., Mussolino, C., Recchia, A., Cathomen, T., & Gonçalves, M. A. F. V. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks1446 · Cited by 312 · see citing works
“Indeed, examples of both physiological and functionimpairing processes associated with instability of tandem repeats are copious and cover virtually all biological systems from viruses and prokaryotes to eukaryotes (44-46).”
Background
Effects of aging on the male reproductive system
Gunes, S. O., Hekim, N., Arslan, M. A., & Aşçı, R. (2016) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-016-0663-y · Cited by 306 · see citing works
The rise, fall and renaissance of microsatellites in eukaryotic genomes
Buschiazzo, E., & Gemmell, N. J. (2006) · BioEssays · doi:10.1002/bies.20470 · Cited by 295 · see citing works
Epigenetic principles and mechanisms underlying nervous system functions in health and disease
Mehler, M. F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.10.001 · Cited by 292 · see citing works
The genome-wide determinants of human and chimpanzee microsatellite evolutionPreprint
Kelkar, Y., Tyekucheva, S., Chiaromonte, F., & Makova, K. D. (2007) · Genome Research · doi:10.1101/gr.7113408 · Cited by 269 · see citing works
Discovery of Rare Mutations in Populations: TILLING by Sequencing
Tsai, H., Howell, T. A., Nitcher, R., Missirian, V., Watson, B., Ngo, K. J., Lieberman, M. C., Fass, J., Uauy, C., Tran, R. K., et al. (2011) · PLANT PHYSIOLOGY · doi:10.1104/pp.110.169748 · Cited by 268 · see citing works
“3B), correspond to simple sequences, which are known to be prone to replication-dependent errors (Pearson et al., 2005).”
Background
Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion
Xi, Z., Zinman, L. H., Moreno, D., Schymick, J. C., Liang, Y., Sato, C., Zheng, Y., Ghani, M., Dib, S., Keith, J. L., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.04.017 · Cited by 267 · see citing works
Metal complexes as structure-selective binding agents for nucleic acids
Keene, F. R., Smith, J. A., & Collins, J. G. (2009) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2009.01.004 · Cited by 254 · see citing works
Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries
Sun, J. H., Zhou, L., Emerson, D. J., Phyo, S. A., Titus, K. R., Gong, W., Gilgenast, T. G., Beagan, J. A., Davidson, B. L., Tassone, F., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.005 · Cited by 249 · see citing works
“Studies in model organisms show that mutations in genes encoding key machinery involved in DNA replication, repair, and recombination are linked to STR instability (Iyer et al., 2015; McMurray, 2010; Mirkin, 2007; Pearson et al., 2005).”
BackgroundInfluential
Recombination: an underappreciated factor in the evolution of plant genomes
Gaut, B. S., Wright, S., Rizzon, C., Dvořák, J., & Anderson, L. K. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1970 · Cited by 247 · see citing works
“Although recombination is known to contribute to gross chromosomal rearrangements, changes in the copy number of repeats and even microsatellite instability”
Background
Mendelian disorders deserve more attention
Antonarakis, S. E., & Beckmann, J. S. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1826 · Cited by 241 · see citing works
CAG Expansion in the Huntington Disease Gene Is Associated with a Specific and Targetable Predisposing Haplogroup
Warby, S. C., Montpetit, A., Hayden, A. R., Carroll, J. B., Butland, S. L., Visscher, H., Collins, J. A., Semaka, A., Hudson, T. J., & Hayden, M. R. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.02.003 · Cited by 237 · see citing works
“Many factorsare believed to contribute toCAGinstability, including the size of the CAG tract, CAG tract interruptions, sex and age of the transmitting parent, environmental influences,(6,7) and other genetic cis-elements and trans-factors.(8,9) Although a larger CAG tract size and transmission through the male germlin…”
Background
Oxidative Stress and Huntington’s Disease: The Good, the Bad, and the Ugly
Kumar, A., & Ratan, R. R. (2016) · Journal of Huntington s Disease · doi:10.3233/jhd-160205 · Cited by 236 · see citing works
“repeats [98].”
DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases
Bettencourt, C., Hensman‐Moss, D., Flower, M., Wiethoff, S., Brice, A., Goizet, C., Stevanin, G., Koutsis, G., Karadima, G., Panas, M., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24656 · Cited by 227 · see citing works
R Loops and Links to Human Disease
Richard, P., & Manley, J. L. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.08.031 · Cited by 218 · see citing works
“These include Huntington's disease [CAG repeats in huntingtin (HTT)], myotonic dystrophy type 1 [CTG repeats in dystrophia myotonica protein kinase (DMPK)], spinocerebellar ataxia type 1 [CAG repeats in ataxin 1 (ATXN1)], fragile X mental retardation or fragile X syndrome (FXS) [CGG repeats in fragile X mental retarda…”
Background
Mutational Dynamics of Microsatellites
Bhargava, A., & Fuentes, F. (2009) · Molecular Biotechnology · doi:10.1007/s12033-009-9230-4 · Cited by 226 · see citing works
“Transcription also influences microsatellite mutation rates through alterations of DNA structure or interference with replication [47, 48].”
Background
Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain
Shelbourne, P., Keller-McGandy, C. E., Bi, W. L., Yoon, S., Dubeau, L., Veitch, N., Vonsattel, J. P., Wexler, N. S., Arnheim, N., & Augood, S. J. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm054 · Cited by 219 · see citing works
“Importantly, the neuronal data from both species provide additional support for the hypothesis that posits the involvement of inappropriate mismatch repair rather than replication in the mechanism responsible for mutation expansion in somatic tissues such as the brain [for a more in-depth discussion of the possible me…”
Accurate de novo and transmitted indel detection in exome-capture data using microassembly
Narzisi, G., O'Rawe, J., Iossifov, I. H., Fang, H., Lee, Y.-H., Wang, Z., Wu, Y., Lyon, G. J., Wigler, M. H., & Schatz, M. C. (2014) · Nature Methods · doi:10.1038/nmeth.3069 · Cited by 216 · see citing works
RNA-dominant diseases
Osborne, R. J., & Thornton, C. A. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl181 · Cited by 213 · see citing works
Epigenetic regulation of heterochromatic DNA stability
Peng, J. C., & Karpen, G. H. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.01.021 · Cited by 209 · see citing works
Disease-associated repeat instability and mismatch repair
Schmidt, M. H. M., & Pearson, C. E. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.11.008 · Cited by 209 · see citing works
“Typically, (CAG)•(CTG) repeats expand, but rare DM1, HD, SCA1 and SBMA families display high levels of contraction of the expanded repeat (reviewed in [3]).”
Background
Myotonic dystrophy: Emerging mechanisms for DM1 and DM2
Cho, D. H., & Tapscott, S. J. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.05.013 · Cited by 203 · see citing works
“Many of the disorders also show a clear propensity for inheritance of a more severe disease phenotype with increasing penetrance than previous generations, termed anticipation [2,3].”
Background
The expanding biology of the C9orf72 nucleotide repeat expansion in neurodegenerative disease
Haeusler, A. R., Donnelly, C. J., & Rothstein, J. D. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.38 · Cited by 205 · see citing works
Short tandem repeats bind transcription factors to tune eukaryotic gene expression
Horton, C. A., Alexandari, A. M., Hayes, M. G. B., Marklund, E., Schaepe, J. M., Aditham, A. K., Shah, N., Suzuki, P., Shrikumar, A., Afek, A., et al. (2023) · Science · doi:10.1126/science.add1250 · Cited by 199 · see citing works
The Genetics of Pulmonary Arterial Hypertension
Austin, E. D., & Loyd, J. E. (2014) · Circulation Research · doi:10.1161/circresaha.115.303404 · Cited by 193 · see citing works
Heterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation
Peng, J. C., & Karpen, G. H. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000435 · Cited by 183 · see citing works
“Chromatin functions in the DNA damage response provokes questions about whether the distinct compositions of euchromatin and heterochromatin impact DNA integrity. Replication across repeated sequences can result in sequence alterations and replication fork stalling and collapse, which can lead to DSBs. In addition, re…”
Background
DNA synthesis by Pol η promotes fragile site stability by preventing under-replicated DNA in mitosis
Bergoglio, V., Boyer, A.-S., Walsh, E. M., Naim, V., Legube, G., Lee, M., Rey, L., Rosselli, F., Cazaux, C., Eckert, K. A., et al. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201207066 · Cited by 182 · see citing works
“…formed within expanded microsatellites stall replication fork progression in vivo, and a causal link between non-B DNA structure formation, replication fork stalling, and genome instability has been demonstrated in microsatellite expansion disease etiology (Pearson et al., 2005; Mirkin, 2007).”
C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD
Liu, E. Y., Russ, J., Wu, K., Neal, D., Suh, E., McNally, A. G., Irwin, D. J., Van Deerlin, V. M., & Lee, E. B. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1286-y · Cited by 180 · see citing works
“rANT aggregates have been proposed to be toxic [2, 46], perhaps through disruption of cellular pathways like autophagy or altered proteostasis [9, 50].”
Reversion of FMR1 methylation and silencing by editing the triplet repeats in Fragile X iPSC-derived neurons
Park, C.-Y., Halevy, T., Lee, D. R., Sung, J. J., Lee, J. S., Yanuka, O., Benvenisty, N., & Kim, D.-W. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.084 · Cited by 178 · see citing works
“Trinucleotide repeat expansions play a role in several neurological, neurodegenerative, and neuromuscular disorders such as Huntington’s disease, FXS, spinocerebellar ataxia, andmyotonic dystrophy (Pearson et al., 2005).”
BackgroundInfluential
The role of variable DNA tandem repeats in bacterial adaptation
Zhou, K., Aertsen, A., & Michiels, C. W. (2013) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12036 · Cited by 175 · see citing works
Repeat instability during DNA repair: Insights from model systems
Usdin, K., House, N. C. M., & Freudenreich, C. H. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2014.999192 · Cited by 174 · see citing works
“…by a GAA expansion in the first intron of the frataxin (FXN) gene (Table 1; note: the repeat on the coding strand is used to refer to the disease-causing repeat for a particular locus) (reviewed in Gatchel & Zoghbi, 2005; Lopez et al., 2010; McMurray, 2010; Mirkin, 2006; Pearson et al., 2005).”
Background
The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity.
Camnasio, S., Carri, A. D., Lombardo, A., Grad, I., Mariotti, C., Castucci, A., Rozell, B., Riso, P. L., Castiglioni, V., Zuccato, C., et al. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.042 · Cited by 181 · see citing works
MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice
Tomé, S., MANLEY, K. M., Simard, J. P., Clark, G. W., Slean, M. M., Swami, M., Shelbourne, P., Tillier, E. R. M., Monckton, D. G., Messer, A. C., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003280 · Cited by 171 · see citing works
“Repeat length, sequence of repeat, purity of the repeat, genomic context and DNA metabolizing proteins can contribute to patterns of repeat instability in mouse models of trinucleotide repeat diseases such as DM1, HD and SCA7 [19].”
BackgroundInfluential
HTT haplotypes contribute to differences in Huntington disease prevalence between Europe and East Asia
Warby, S. C., Visscher, H., Collins, J. A., Doty, C. N., Carter, C., Butland, S. L., Hayden, A. R., Kanazawa, I., Ross, C. J., & Hayden, M. R. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.229 · Cited by 167 · see citing works
Transcription promotes contraction of CAG repeat tracts in human cells
Lin, Y., Dion, V., & Wilson, J. H. (2006) · Nature Structural &Molecular Biology · doi:10.1038/nsmb1042 · Cited by 169 · see citing works
FAN1 modifies Huntington’s disease progression by stabilizing the expanded HTT CAG repeat
Goold, R., Flower, M. D., Moss, D. J. H., Medway, C., Wood‐Kaczmar, A., André, R., Farshim, P. P., Bates, G. P., Holmans, P., Jones, L., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy375 · Cited by 151 · see citing works
“Longer CAG repeats are more unstable and prone to increased rates of expansion (35), a feature recapitulated in our U20S cells expressing HTT exon 1 with a series of CAG repeat lengths (Fig.”
Background
Msh3 is a limiting factor in the formation of intergenerational CTG expansions in DM1 transgenic mice
Foiry, L., Dong, L., Savouret, C., Hubert, L., Riele, H. T., Junien, C., & Gourdon, G. (2006) · Human Genetics · doi:10.1007/s00439-006-0164-7 · Cited by 151 · see citing works
“Since the discovery in 1991 that the expansion of unstable trinucleotide repeats (TNR) can cause disease, multiple disorders have been shown to be associated with expanded microsatellites, mostly CNG trinucleotides (Pearson et al. 2005).”
Background
Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues
López, A., Nakamori, M., Tomé, S., Chitayat, D. A., Gourdon, G., Thornton, C. A., & Pearson, C. E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq427 · Cited by 149 · see citing works
“Such a relation exists in FRAXA in which evidence suggests that the presence of DNA methylation protects against contractions of expanded CGG tracts (63,80).”
Functional Mechanisms of Microsatellite DNA in Eukaryotic Genomes
Bagshaw, A. (2017) · Genome Biology and Evolution · doi:10.1093/gbe/evx164 · Cited by 151 · see citing works
Replication-dependent instability at (CTG)•(CAG) repeat hairpins in human cells
Liu, G., Chen, X., Bissler, J. J., Sinden, R. R., & Leffak, M. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.416 · Cited by 149 · see citing works
“In individuals with DM1, instability of the (CTG)•(CAG) repeats at the DMPK locus is evident during germ cell development and in somatic cell”
Background
Mechanism of a genetic glissando*: structural biology of indel mutations
García–Díaz, M., & Kunkel, T. A. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.02.004 · Cited by 149 · see citing works
A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo
Nakamori, M., Panigrahi, G. B., Lanni, S., Gall-Duncan, T., Hayakawa, H., Tanaka, H., Luo, J., Otabe, T., Li, J., Sakata, A., et al. (2020) · Nature Genetics · doi:10.1038/s41588-019-0575-8 · Cited by 147 · see citing works
Genome-Wide Analysis of Histidine Repeats Reveals Their Role in the Localization of Human Proteins to the Nuclear Speckles Compartment
Salichs, E., Ledda, A., Mularoni, L., Albà, M. M., & de la Luna, S. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000397 · Cited by 147 · see citing works
“repeats (for review, see [8]).”
ARX: a gene for all seasons
Gécz, J., Cloosterman, D., & Partington, M. W. (2006) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.04.003 · Cited by 147 · see citing works
“Alternatively, DNA replication- or DNA repair-based mechanisms similar to those proposed for dynamic mutations might be involved [17].”
Background
Stoichiometry of Base Excision Repair Proteins Correlates with Increased Somatic CAG Instability in Striatum over Cerebellum in Huntington's Disease Transgenic Mice
Goula, A.-V., Berquist, B. R., Wilson, D. M., Wheeler, V. C., Trottier, Y., & Mérienne, K. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000749 · Cited by 145 · see citing works
“transcription contribute to instability of CAG/CTG repeats, although the underlying mechanisms remain elusive [10].”
Background
CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination
Libby, R. T., Hagerman, K. A., Pineda, V. V., Lau, R., Cho, D. H., Baccam, S. L., Axford, M. M., Cleary, J. D., Moore, J. M., Sopher, B. L., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000257 · Cited by 138 · see citing works
“This tissue-specific instability, or ‘‘somatic mosaicism’’, occurs in human patients with repeat diseases, and in mouse models of repeat instability and disease [1,8,11].”
Background
Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats
Reddy, K., Tam, M., Bowater, R. P., Barber, M., Tomlinson, M. J., Edamura, K. N., Wang, Y., & Pearson, C. E. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq935 · Cited by 140 · see citing works
“Expansion of (CAG) (CTG) tracts, where the CAG strand is transcribed, is responsible for at least nine polyglutamine diseases, including Huntington’s disease, spinocerebellar ataxia types 1–3, 6, 7, 8, 17 (SCA1, etc.), and spinal bulbar muscular atrophy (SBMA) (6).”
Influential
Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers
Nolin, S. L., Glicksman, A., Ersalesi, N., Dobkin, C., Brown, W. T., Cao, R., Blatt, E. B., Sah, S., Latham, G. J., & Hadd, A. G. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.106 · Cited by 139 · see citing works
Trinucleotide repeats in human genome and exome
Kozłowski, P., de Mezer, M., & Krzyżosiak, W. J. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq127 · Cited by 140 · see citing works
“More than 20 genetic disorders belong to this group; they are mostly neurodegenerative and neuromuscular (10,11) disorders.”
Background
Large-scale expansions of Friedreich’s ataxia GAA repeats in yeast
Shishkin, A. A., Voineagu, I., Matera, R., Cherng, N., Chernet, B. T., Krasilnikova, M., Narayanan, V., Lobachev, K., & Mirkin, S. (2009) · Molecules and Cells · doi:10.1016/j.molcel.2009.06.017 · Cited by 143 · see citing works
“…strand misalignment promoted by the stable secondary structures during one of those processes is believed to be central for repeat instability (reviewed in McMurray, 1999; 82 Molecular Cell 35, 82–92, July 10, 2009 ª2009 Elsevier Inc. Mirkin, 2006; Pearson et al., 2005; Wells et al., 2005).”
Background
Delivery and therapeutic applications of gene editing technologies ZFNs, TALENs, and CRISPR/Cas9
LaFountaine, J. S., Fathe, K., & Smyth, H. D. C. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.08.029 · Cited by 137 · see citing works
What Is a Microsatellite: A Computational and Experimental Definition Based upon Repeat Mutational Behavior at A/T and GT/AC Repeats
Kelkar, Y., Strubczewski, N., Hile, S. E., Chiaromonte, F., Eckert, K. A., & Makova, K. D. (2010) · Genome Biology and Evolution · doi:10.1093/gbe/evq046 · Cited by 133 · see citing works
CREB-Binding Protein Modulates Repeat Instability in a Drosophila Model for PolyQ Disease
Jung, J., & Bonini, N. M. (2007) · Science · doi:10.1126/science.1139517 · Cited by 133 · see citing works
Echinodermata: The Complex Immune System in Echinoderms
Smith, L. C., Arizza, V., Hudgell, M. A. B., Barone, G., Bodnar, A. G., Buckley, K. M., Cunsolo, V., Dheilly, N. M., Franchi, N., Fugmann, S. D., et al. (2018) · Springer eBooks · doi:10.1007/978-3-319-76768-0_13 · Cited by 131 · see citing works
“This repetitive structure may contribute to gene diversification by promoting genomic instability, as has been noted in other systems (Pearson et al. 2005; Thys et al. 2014), perhaps through SpTrf gene deletion and by blocking the progression of sequence homogenization of clustered genes from gene conversion (Miller e…”
Background
CTCF Regulates Ataxin-7 Expression through Promotion of a Convergently Transcribed, Antisense Noncoding RNA
Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., & Spada, A. R. L. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.027 · Cited by 126 · see citing works
Predictive testing for Huntington disease: interpretation and significance of intermediate alleles
Semaka, A., Creighton, S., Warby, S. C., & Hayden, M. R. (2006) · Clinical Genetics · doi:10.1111/j.1399-0004.2006.00668.x · Cited by 129 · see citing works
“Germline repeat instability is observed in all trinucleotide disorders (22).”
BackgroundInfluential
Analysis of somatic microsatellite indels identifies driver events in human tumors
Maruvka, Y. E., Mouw, K. W., Karlić, R., Parasuraman, P., Kamburov, A., Polak, P. P., Haradhvala, N. J., Hess, J. M., Rheinbay, E., Brody, Y., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3966 · Cited by 124 · see citing works
Structural Diversity of Triplet Repeat RNAs
Sobczak, K., Michlewski, G., de Mezer, M., Kierzek, E., Krol, J., Olejniczak, M., Kierzek, R., & Krzyżosiak, W. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.078790 · Cited by 128 · see citing works
Epigenetic mechanisms and genome stability
Putiri, E. L., & Robertson, K. D. (2010) · Clinical Epigenetics · doi:10.1007/s13148-010-0017-z · Cited by 124 · see citing works
“, DNA hairpins), particularly during replication, transcription, and DNA repair (Pearson et al. 2005).”
Background
Repeat‐associated non‐AUG translation in C9orf72‐ALS/FTD is driven by neuronal excitation and stress
Westergard, T., McAvoy, K. J., Russell, K. A., Wen, X., Pang, Y., Verdone, B. M., Pasinelli, P., Trotti, D., & Haeusler, A. R. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809423 · Cited by 126 · see citing works
“NREs have been associated with over 30 neurological and neuromuscular disorders (Pearson et al, 2005; McMurray, 2010).”
Background
Genome plasticity in Candida albicans is driven by long repeat sequences
Todd, R. T., Wikoff, T. D., Forche, A., & Selmecki, A. (2019) · eLife · doi:10.7554/elife.45954 · Cited by 118 · see citing works
Roles of DNA Polymerases in Replication, Repair, and Recombination in Eukaryotes
Pavlov, Y. I., Shcherbakova, P. V., & Rogozin, I. B. (2006) · International Review of Cytology · doi:10.1016/s0074-7696(06)55002-8 · Cited by 123 · see citing works
Myotonic dystrophy: disease repeat range, penetrance, age of onset, and relationship between repeat size and phenotypes
Yum, K., Wang, E. T., & Kalsotra, A. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.01.007 · Cited by 123 · see citing works
“Furthermore, the rate of expansion in somatic cells can vary within the same tissue [8].”
Transcription-Induced CAG Repeat Contraction in Human Cells Is Mediated in Part by Transcription-Coupled Nucleotide Excision Repair
Lin, Y., & Wilson, J. H. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00739-07 · Cited by 120 · see citing works
“For neurons, which no longer divide, the ongoing instability of their repeats cannot depend on DNA replication, a process often suggested as the primary mechanism for germ line instability (20, 53).”
BackgroundInfluential
Intron retention induced by microsatellite expansions as a disease biomarker
Sznajder, Ł. J., Thomas, J. D., Carrell, E. M., Reid, T. S., McFarland, K. N., Cleary, J. D., Oliveira, R., Nutter, C. A., Bhatt, K. S., Sobczak, K., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716617115 · Cited by 121 · see citing works
“While GC-rich trinucleotide expansions (exp) predominate in exonic regions, intron mutations are composed of 3- to 6-bp repeats that vary considerably in GC content (20–100%) (6, 8).”
Background
Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin
Velázquez‐Pérez, L., Cruz, G. S., Santos, N., Mederos, L. E. A., Batallán, K. E., Rodríguez‐Labrada, R., Paneque, M., Mesa, J. M. L., Díaz, J. C. R., Rodríguez, R. A., et al. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.03.015 · Cited by 121 · see citing works
Extensive size variability of the GGGGCC expansion in C9orf72 in both neuronal and non-neuronal tissues in 18 patients with ALS or FTD
Nordin, A., Akimoto, C., Wuolikainen, A., Alstermark, H., Jonsson, P., Birve, A., Marklund, S. L., Graffmo, K. S., Forsberg, K., Brännström, T., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv064 · Cited by 120 · see citing works
“Similar observations have been made in trinucleotide-repeat expansion disorders, where expansions in the cerebellum have been found to be shorter than in other brain regions (24).”
Result
Detection of structural variants and indels within exome data
Karakoç, E., Alkan, C., O’Roak, B. J., Dennis, M. Y., Vives, L., Mark, K. M. K., Rieder, M. J., Nickerson, D. A., & Eichler, E. E. (2011) · Nature Methods · doi:10.1038/nmeth.1810 · Cited by 118 · see citing works
“Such regions are subject to higher mutation rates, due in part to their greater potential for replication slippage 14 .”
The Intra-S Checkpoint Responses to DNA Damage
Iyer, D., & Rhind, N. (2017) · Genes · doi:10.3390/genes8020074 · Cited by 113 · see citing works
“Replication stress can also be caused be intrinsically difficult to replicate sequences in the genome, such as G-quadruplexes and repeats, which can lead to replication fork slippage and chromosomal breaks [3,4,15].”
Background

23 DNA Replication, Repeat Instability, and Human DiseasePreprint
Cleary, J. D., Pearson, C. E., & Spada, A. R. L. (2006) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969766.47.461 · Cited by 1 · see citing works
Mystery of Expansion: DNA Metabolism and Unstable Repeats
Grishchenko, I. V., Purvinsh, Y. V., & Yudkin, D. V. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-41283-8_7 · Cited by 4 · see citing works
Instability of the DNA repeats mutation in humans hereditary disorders
Zhao, H., Zhao, Y., Chai, R., & Cai, L. (2011) · International Conference on Remote Sensing, Environment and Transportation Engineering · doi:10.1109/rsete.2011.5965950
Dynamic mutations: a decade of unstable expanded repeats in human genetic disease
Richards, R. I. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.20.2187 · Cited by 112 · see citing works
Repeat instability during DNA repair: Insights from model systems
Usdin, K., House, N. C. M., & Freudenreich, C. H. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2014.999192 · Cited by 174 · see citing works

Authors: Pearson, C. E., Edamura, K. N., & Cleary, J. D.
Affiliations: University of Toronto (CA)
Hospital for Sick Children (CA)
Corresponding author: Pearson, Christopher E.
ORCID: Pearson, Christopher E.
Venue: Nature Reviews Genetics
Publisher: Springer Science and Business Media LLC
Published: 2005-10
Volume: 6
Issue: 10
Pages: 729-742
ISSN: 1471-0056 (ISSN-L)
1471-0064
DOI: 10.1038/nrg1689
OpenAlex: W2087505473
Cited by: 924
References: 157
Citations by year: 2026: 13 · 2025: 23 · 2024: 45 · 2023: 29 · 2022: 25 · 2021: 54 · 2020: 27 · 2019: 38 · 2018: 53 · 2017: 45 · 2016: 58 · 2015: 41 · 2014: 55 · 2013: 46 · 2012: 56
FWCI: 3.89
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords: repeat instability, dynamic mutation, trinucleotide repeat disorders, neurodegenerative diseases, neuromuscular disorders, cis-regulatory elements, trans-acting proteins, DNA replication, DNA repair, DNA recombination, DNA secondary structure
MeSH terms: DNA Repair, DNA Replication, Humans, Models, Genetic, Mutation, Recombination, Genetic, Trinucleotide Repeat Expansion, Heredodegenerative Disorders, Nervous System, DNA Repeat Expansion, Genomic Instability

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Repeat instability: mechanisms of dynamic mutations

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks