A nervous predisposition to unrepaired DNA double strand breaks

Reynolds, John J.; Stewart, Grant S.

doi:10.1016/j.dnarep.2013.04.011

Cited by 26DNA Repair MechanismsGenetic Neurodegenerative DiseasesEffects of Radiation Exposure

A nervous predisposition to unrepaired DNA double strand breaks

Reynolds, John J., Stewart, Grant S.·2013·DNA Repair

DOI 10.1016/j.dnarep.2013.04.011

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Abstract

Ataxia-telangiectasia (A-T) has for a long time stood apart from most other human neurodegenerative syndromes by the characteristic failure of cells derived from these patients to properly repair DNA damage-induced by ionizing radiation. The discovery of mutations in the ATM gene as being the underlying cause for A-T and the demonstration that the ATM protein functions as a DNA damage-responsive kinase has defined current research focusing on decoding how the cell responds to genotoxic stress. Yet, despite significant advances in delineating the cellular DNA damage response pathways coordinated by ATM, very little headway has been made toward understanding how loss of ATM leads to progressive cerebellar ataxia and whether this can be attributed to an underlying defect in DNA double strand break repair (DSBR). Since its identification, A-T has been used as the archetypal model for how a deficiency in DNA repair affects both the development and maintenance of the nervous and immune systems in humans as well as contributing to the process of tumourigenesis. However, following the growing availability and cost effectiveness of next generation sequencing technologies, the increasing recognition of novel human disorders associated with abnormal DNA repair has demonstrated that the neuropathology typified by A-T is an 'exception' rather than the 'rule'. As a consequence, this throws into doubt the longstanding hypothesis that the neurodegeneration seen in A-T is due to the progressive loss of damaged neurons that have acquired toxic levels of unrepaired DNA lesions over time. Therefore, this review aims to address the question: Is defective DNA double strand break repair an underlying cause of neurodegeneration?

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Ataxia telangiectasia results from a mutation in the ATM DNA damage sensing kinase.
“One of the aging syndromes, ataxia telangiectasia (AT), results from a genetic defect in the DNA damage sensing kinase ataxia telangiectasia mutated (ATM) [72,73].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [72]

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A Murine Model of Nijmegen Breakage Syndrome
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The Mre11:Rad50 Structure Shows an ATP-Dependent Molecular Clamp in DNA Double-Strand Break Repair
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Beyond ATM: The protein kinase landscape of the DNA damage response
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Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70
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Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks
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Autophosphorylation and ATM Activation
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Mutations associated with variant phenotypes in ataxia-telangiectasia.
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Localization of a Portion of Extranuclear ATM to Peroxisomes
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Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation
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The role of homologous recombination in radiation-induced double-strand break repair
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RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling
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Self-citation
Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development
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NEK1 Mutations Cause Short-Rib Polydactyly Syndrome Type Majewski
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A Supramodular FHA/BRCT-Repeat Architecture Mediates Nbs1 Adaptor Function in Response to DNA Damage
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Clinical spectrum of ataxia-telangiectasia in adulthood
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Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: A genotype-phenotype study
Verhagen, M. M. M., Last, J. I. K., Hogervorst, F. B. L., Smeets, D., Roeleveld, N., Verheijen, F. W., Catsman‐Berrevoets, C. E., Wulffraat, N. M., Cobben, J. M., Hiel, J. A. P., et al. (2011) · Human Mutation · doi:10.1002/humu.22016 · Cited by 175 · see citing works
Targeted disruption of NBS1 reveals its roles in mouse development and DNA repair
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An essential function for NBS1 in the prevention of ataxia and cerebellar defects
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Alterations in G1 to S Phase Cell-Cycle Regulators during Amyotrophic Lateral Sclerosis
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MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks
Wu, L., Luo, K., Lou, Z., & Chen, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802885105 · Cited by 156 · see citing works
Identification and functional consequences of a novel MRE11 mutation affecting 10 Saudi Arabian patients with the ataxia telangiectasia-like disorder
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Regulation of DNA strand exchange in homologous recombination
Holthausen, J. T., Wyman, C., & Kanaar, R. (2010) · DNA repair · doi:10.1016/j.dnarep.2010.09.014 · Cited by 136 · see citing works
Loss of Neuronal Cell Cycle Control in Ataxia-Telangiectasia: A Unified Disease Mechanism
Yang, Y. F., & Herrup, K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4946-04.2005 · Cited by 130 · see citing works
Cytoplasmic ATM in Neurons Modulates Synaptic Function
Li, J., Han, Y. R., Plummer, M. R., & Herrup, K. (2009) · Current Biology · doi:10.1016/j.cub.2009.10.039 · Cited by 130 · see citing works
The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex
Stracker, T. H., Morales, M., Couto, S. S., Hussein, H., & Petrini, J. H. J. (2007) · Nature · doi:10.1038/nature05740 · Cited by 127 · see citing works
Distinct functional domains of Nbs1 modulate the timing and magnitude of ATM activation after low doses of ionizing radiation
Hořejšı́, Z., Falck, J., Bakkenist, C. J., Kastan, M. B., Lukas, J., & Bártek, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207447 · Cited by 125 · see citing works
Ataxia-Telangiectasia: Phenotype/Genotype Studies of ATM Protein Expression, Mutations, and Radiosensitivity
Becker-Catania, S. G., Chen, G., Hwang, M. J., Wang, Z., Sun, X., Sanal, Ö., Bernatowska, E. A., Chessa, L., Lee, E. Y.-H. P., & Gatti, R. A. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.2998 · Cited by 123 · see citing works
MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder
Delia, D. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh221 · Cited by 120 · see citing works
CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1
Quennet, V., Beucher, A., Barton, O., Takeda, S., & Löbrich, M. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1175 · Cited by 120 · see citing works
CtIP Mutations Cause Seckel and Jawad Syndromes
Qvist, P., Huertas, P., Jimeno, S., Nyegaard, M., Hassan, M. J., Jackson, S. P., & Børglum, A. D. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002310 · Cited by 120 · see citing works
Mre11 regulates CtIP-dependent double-strand break repair by interaction with CDK2
Buis, J. M., Stoneham, T., Spehalski, E. I., & Ferguson, D. O. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2212 · Cited by 113 · see citing works
CDK targeting of NBS1 promotes DNA‐end resection, replication restart and homologous recombination
Falck, J., Forment, J. V., Coates, J., Mistrík, M., Lukas, J., Bártek, J., & Jackson, S. P. (2012) · EMBO Reports · doi:10.1038/embor.2012.58 · Cited by 108 · see citing works
Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBSPreprint
Shull, E. R. P., Lee, Y., Nakane, H., Stracker, T. H., Zhao, J., Russell, H. R., Petrini, J. H. J., & McKinnon, P. J. (2009) · Genes & Development · doi:10.1101/gad.1746609 · Cited by 104 · see citing works
Degeneration of neurons, synapses, and neuropil and glial activation in a murine Atm knockout model of ataxia–telangiectasia
Kuljiš, R. O., Xu, Y., Aguila, M. C., & Baltimore, D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12688 · Cited by 100 · see citing works
The Rad50 coiled-coil domain is indispensable for Mre11 complex functions
Hohl, M., Kwon, Y., Muñoz-Galván, S., Xue, X., Tous, C., Aguilera, A., Sung, P., & Petrini, J. H. J. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2116 · Cited by 99 · see citing works
Quantitative neurologic assessment of ataxia-telangiectasia
Crawford, T. O., Mandir, A. S., Lefton‐Greif, M. A., Goodman, S. N., Goodman, B. K., Sengul, H. S., & Lederman, H. M. (2000) · Neurology · doi:10.1212/wnl.54.7.1505 · Cited by 96 · see citing works
Coping with DNA double strand breaks
Hiom, K. J. (2010) · DNA repair · doi:10.1016/j.dnarep.2010.09.018 · Cited by 94 · see citing works
Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia
Devgan, S. S., Sanal, Ö., Doil, C., Nakamura, K., Nahas, S., Pettijohn, K. J., Bártek, J., Lukas, C., Lukáš, J., & Gatti, R. A. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.18 · Cited by 88 · see citing works
Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability
Seemanová, E., Sperling, K., Neitzel, H., Varon, R., Hadač, J., Butova, O., Schröck, E., Seeman, P., & Digweed, M. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2005.035287 · Cited by 86 · see citing works
Brca2, Rad51 and Mre11: Performing balancing acts on replication forks
Costanzo, V. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.07.009 · Cited by 77 · see citing works
hMRE11: genomic structure and a null mutation identified in a transcript protected from nonsense-mediated mRNA decay
Pitts, S. A. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.11.1155 · Cited by 75 · see citing works
Two Brothers with Ataxia-Telangiectasia-like Disorder with Lung Adenocarcinoma
Uchisaka, N., Takahashi, N., Sato, M., Kikuchi, A., Mochizuki, S., Imai, K., Nonoyama, S., Ohara, O., Watanabe, F., Mizutani, S., et al. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2009.02.037 · Cited by 69 · see citing works
Neuropathology in classical and variant ataxia‐telangiectasia
Verhagen, M. M. M., Martin, J., van Deuren, M., Groote, C. C., Weemaes, C. M. R., Kremer, B. H. P. H., Taylor, A. M. R., Willemsen, M. A. A. P., & Lammens, M. M. Y. (2011) · Neuropathology · doi:10.1111/j.1440-1789.2011.01263.x · Cited by 67 · see citing works
Requirement for DNA Ligase IV during Embryonic Neuronal Development
Gatz, S. A., Ju, L., Gruber, R., Hoffmann, E. R., Carr, A. M., Wang, Z.-Q., Liu, C., & Jeggo, P. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1324-11.2011 · Cited by 67 · see citing works
NEK1 and DYNC2H1 are both involved in short rib polydactyly Majewski type but not in Beemer Langer cases
Hokayem, J. E., Huber, C., Couvé, A., Aziza, J., Baujat, G., Bouvier, R., Cavalcanti, D. P., Collins, F. A., Cordier, M., Delezoide, A., et al. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2011-100717 · Cited by 67 · see citing works
Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly
Matsumoto, Y., Miyamoto, T., Sakamoto, H., Izumi, H., Nakazawa, Y., Ogi, T., Tahara, H., Oku, S., Hiramoto, A., Shiiki, T., et al. (2011) · DNA repair · doi:10.1016/j.dnarep.2010.12.002 · Cited by 62 · see citing works
A new locus for Seckel syndrome on chromosome 18p11.31-q11.2
Børglum, A. D., Balslev, T., Haagerup, A., Birkebæk, N., Binderup, H. G., Kruse, T. A., & Hertz, J. M. (2001) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200701 · Cited by 61 · see citing works
ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome.
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Adult‐onset ataxia telangiectasia due to ATM 5762ins137 mutation homozygosity
Sutton, I. J., Last, J. I. K., Ritchie, S. J., Harrington, H. J., Byrd, P. J., & Taylor, A. M. R. (2004) · Annals of Neurology · doi:10.1002/ana.20139 · Cited by 59 · see citing works
Further support for digenic inheritance in Bardet-Biedl syndrome
Fauser, S., Munz, M., & Besch, D. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.8.e104 · Cited by 55 · see citing works
Ataxia‐telangiectasia: Mild neurological presentation despite null ATM mutation and severe cellular phenotype
Alterman, N., Fattal‐Valevski, A., Moyal, L., Crawford, T. O., Lederman, H. M., Ziv, Y., & Shiloh, Y. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31853 · Cited by 54 · see citing works
Rad50 Is Dispensable for the Maintenance and Viability of Postmitotic Tissues
Adelman, C. A., De, S., & Petrini, J. H. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01525-08 · Cited by 45 · see citing works
Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia
Byrd, P. J., Srinivasan, V., Last, J. I., Smith, A. J. B., Biggs, P., Carney, E. F., Exley, A., Abson, C., Stewart, G. S., Izatt, L., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.534 · Cited by 44 · see citing works
Self-citation
A divalent FHA/BRCT‐binding mechanism couples the MRE11–RAD50–NBS1 complex to damaged chromatin
Hari, F. J., Spycher, C., Jungmichel, S., Pavic, L., & Stucki, M. (2010) · EMBO Reports · doi:10.1038/embor.2010.30 · Cited by 37 · see citing works
Prematurely Aged Children: Molecular Alterations Leading to Hutchinson-Gilford Progeria and Werner Syndromes
Domínguez‐Gerpe, L., & Araújo‐Vilar, D. (2008) · Current Aging Science · doi:10.2174/1874609810801030202 · Cited by 33 · see citing works
Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype
Dutrannoy, V., Demuth, I., Baumann, U., Schindler, D., Konrat, K., Neitzel, H., Gillessen‐Kaesbach, G., Radszewski, J., Rothe, S., Schellenberger, M. T., et al. (2010) · Human Mutation · doi:10.1002/humu.21315 · Cited by 33 · see citing works
New mutations in the ATM gene and clinical data of 25 AT patients
Demuth, I., Dutrannoy, V., Marques, W., Neitzel, H., Schindler, D., Dimova, P. S., Chrzańowska, K., Bojinova, V., Gregorek, H., Graul-Neumann, L. M., et al. (2011) · Neurogenetics · doi:10.1007/s10048-011-0299-0 · Cited by 30 · see citing works
ATM immunolocalization in mouse neuronal endosomes: implications for ataxia-telangiectasia
Kuljiš, R. O., Chen, G., Lee, E. Y.-H. P., Aguila, M. C., & Xu, Y. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01813-2 · Cited by 29 · see citing works
Fertility defects revealing germline biallelic nonsense NBN mutations
Warcoin, M., Lespinasse, J., Despouy, G., d’Enghien, C. D., Laugé, A., Portnoï, M., Christin‐Maître, S., Stoppa‐Lyonnet, D., & Stern, M. (2008) · Human Mutation · doi:10.1002/humu.20904 · Cited by 26 · see citing works
A syndromic form of autosomal recessive congenital microcephaly (Jawad syndrome) maps to chromosome 18p11.22–q11.2
Hassan, M. J., Chishti, M. S., Jamal, S. M., Tariq, M., & Ahmad, W. (2007) · Human Genetics · doi:10.1007/s00439-007-0452-x · Cited by 26 · see citing works
Allelic imbalance within the E-cadherin gene is an infrequent event in prostate carcinogenesis
Murant, S. J., Rolley, N., Phillips, S. M. A., Stower, M. J., & Maitland, N. J. (2000) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(200001)27:1 · Cited by 12 · see citing works

Flagged first, then by citations

Sorted by citations

T-cell aging in rheumatoid arthritis
Weyand, C. M., Yang, Z., & Goronzy, J. J. (2014) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000011 · Cited by 164 · see citing works
“Patients with RA have ATM-deficient T cells which accumulate DNA breaks and fail to efficiently repair radiationinduced DNA lesions [74].”
BackgroundInfluential
ATM specifically mediates repair of double-strand breaks with blocked DNA ends
Álvarez-Quilón, A., Serrano-Benítez, A., Lieberman, J. A., Quintero, C., Sánchez‐Gutiérrez, D., Escudero, L. M., & Cortés‐Ledesma, F. (2014) · Nature Communications · doi:10.1038/ncomms4347 · Cited by 108 · see citing works
ATM: Expanding roles as a chief guardian of genome stability
Shiloh, Y. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.09.002 · Cited by 107 · see citing works
“Concerns are expressed, however, about attributing the neurodegenerative aspects of A-T solely to the defective DSB response [78].”
Background
Chromatin Regulation of DNA Damage Repair and Genome Integrity in the Central Nervous System
Pan, L., Penney, J., & Tsai, L. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.08.001 · Cited by 48 · see citing works
“However, ataxia telangiectasia and ataxia-telangiectasia-like disease are the exceptions [97,98].”
The cerebellar degeneration in ataxia-telangiectasia: A case for genome instability
Shiloh, Y. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102950 · Cited by 47 · see citing works
Coenzyme A, more than ‘just’ a metabolic cofactor
Srinivasan, B., & Sibon, O. C. M. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140125 · Cited by 44 · see citing works
Ataxia telangiectasia syndrome: moonlighting ATM
Zaki‐Dizaji, M., Akrami, S. M., Abolhassani, H., Rezaei, N., & Aghamohammadi, A. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2017.1392856 · Cited by 41 · see citing works
“Also, other functions of ATM may be more important for maintenance of the cells in cerebellum from uncontrolled cell cycle reentry [256].”
Background
RAD50 phosphorylation promotes ATR downstream signaling and DNA restart following replication stress
Gatei, M. H., Kijas, A. W., Biard, D. S. F., Dörk, T., & Lavin, M. F. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu141 · Cited by 36 · see citing works
“All of these proteins together with ATM respond to DNA DSB but differ in response during development and in the adultnervous system (12).”
Background
RNF8 deficiency results in neurodegeneration in mice
Ouyang, S., Song, Y., Tian, Y., Chen, Y., Yu, X., & Wang, D. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.07.010 · Cited by 35 · see citing works
“Defects in DSB repair have been detected in the cells of several human neurodegenerative syndromes, such as ataxia-telangiectasia (A-T) (Reynolds and Stewart, 2013).”
Background
Novel 2-substituted-quinoxaline analogs with potential antiproliferative activity against breast cancer: insights into cell cycle arrest, topoisomerase II, and EGFR activity
Salem, M. G., El-ata, S. A. A., Elsayed, E. H., Mali, S. N., Alshwyeh, H. A., Almaimani, G., Almaimani, R. A., Almasmoum, H. A., Altwaijry, N., Al-Olayan, E. M., et al. (2023) · RSC Advances · doi:10.1039/d3ra06189b · Cited by 35 · see citing works
Structure of transcribed chromatin is a sensor of DNA damage
Pestov, N. A., Gerasimova, N. S., Kulaeva, O. I., & Studitsky, V. M. (2015) · Science Advances · doi:10.1126/sciadv.1500021 · Cited by 29 · see citing works
Military Personnel with Chronic Symptoms Following Blast Traumatic Brain Injury Have Differential Expression of Neuronal Recovery and Epidermal Growth Factor Receptor Genes
Heinzelmann, M. M., Reddy, S. Y., French, L. M., Wang, D., Lee, H., Barr, T. L., Baxter, T., Mysliwiec, V., & Gill, J. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00198 · Cited by 28 · see citing works
A single strand that links multiple neuropathologies in human disease
Reynolds, J. J., & Stewart, G. S. (2013) · Brain · doi:10.1093/brain/aws310 · Cited by 27 · see citing works
Self-citation
Cdk12 Regulates Neurogenesis and Late-Arising Neuronal Migration in the Developing Cerebral Cortex
Chen, H., Juan, H.-C., Wong, Y., Tsai, J., & Fann, M. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw081 · Cited by 25 · see citing works
RAD6B Plays a Critical Role in Neuronal DNA Damage Response to Resist Neurodegeneration
Guo, Z., Tian, Y., Guo, Y., Li, B., Liu, X., Xie, K., Song, Y., & Wang, D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00392 · Cited by 19 · see citing works
Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders
Kisby, G. E., Wilson, D. M., & Spencer, P. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137221 · Cited by 16 · see citing works
“…post-mitotic neuronal cell loss, or both, is supported by a collection of disorders with inherited mutations in core DNA repair factors, such as ataxia with oculomotor apraxia (AOA) types 1 and 2 and spinocerebellar atrophy with axonal neuropathy type 1 (SCAN1), amongst others [43,44].”
Background
RAD50 regulates mitotic progression independent of DNA repair functions
Völkening, L., Vatselia, A., Asgedom, G., Bastians, H., Lavin, M. F., Schindler, D., Schambach, A., Bousset, K., & Dörk, T. (2019) · The FASEB Journal · doi:10.1096/fj.201902318r · Cited by 15 · see citing works
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Authors: Reynolds, J. J., & Stewart, G. S.
Affiliations: University of Birmingham (GB)
Corresponding author: Stewart, Grant S.
ORCID: Reynolds, John J.
Stewart, Grant S.
Venue: DNA Repair
Publisher: Elsevier BV
Published: 2013-08
Volume: 12
Issue: 8
Pages: 588-599
ISSN: 1568-7856 (ISSN-L)
1568-7864
DOI: 10.1016/j.dnarep.2013.04.011
OpenAlex: W2092119067
Cited by: 26
References: 137
Citations by year: 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 3
FWCI: 0.47
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: DNA repair (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders: Cancer Research UK (13030)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords: ataxia telangiectasia, ATM kinase, DNA double-strand break repair, neurodegeneration, cerebellar ataxia, radiosensitivity, DNA damage response, genotoxic stress, DNA repair disorders, neuronal loss
MeSH terms: Ataxia Telangiectasia, DNA Repair, Growth Disorders, Humans, Microcephaly, Mutation, Nervous System, Neurons, Radiation, Ionizing, Neurodegenerative Diseases, Genetic Predisposition to Disease, DNA Repair-Deficiency Disorders, Nijmegen Breakage Syndrome, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins

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A nervous predisposition to unrepaired DNA double strand breaks

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