Mechanisms and Consequences of Double‐Strand DNA Break Formation in Chromatin
Open accessAbstract
All organisms suffer double‐strand breaks (DSBs) in their DNA as a result of exposure to ionizing radiation. DSBs can also form when replication forks encounter DNA lesions or repair intermediates. The processing and repair of DSBs can lead to mutations, loss of heterozygosity, and chromosome rearrangements that result in cell death or cancer. The most common pathway used to repair DSBs in metazoans (non‐homologous DNA end joining) is more commonly mutagenic than the alternative pathway (homologous recombination mediated repair). Thus, factors that influence the choice of pathways used DSB repair can affect an individual's mutation burden and risk of cancer. This review describes radiological, chemical, and biological mechanisms that generate DSBs, and discusses the impact of such variables as DSB etiology, cell type, cell cycle, and chromatin structure on the yield, distribution, and processing of DSBs. The final section focuses on nucleosome‐specific mechanisms that influence DSB production, and the possible relationship between higher order chromosome coiling and chromosome shattering (chromothripsis). J. Cell. Physiol. 230: 3–14, 2016. © 2015 Wiley Periodicals, Inc.
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SSBs may form DSBs through collision with the transcriptional machinery and replication forks, or through close proximity to another SSB.
“SSBs may form DSBs through their collision with the transcriptional machinery and replication forks, or through their close proximity to another SSB.”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Cannan & Pederson, 2016
DSBs are directly generated by transcription, whereby TOP2 induces transient DSBs to relieve torsional stress and facilitate gene expression.
“DSBs are also directly generated by transcription (Cannan & Pederson, 2016), whereby topoisomerase II (TOP2) induces transient DSBs to relieve torsional stress and facilitate gene expression.”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Cannan & Pederson, 2016
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Semenenko, V. A., & Stewart, R. D. (2004) · Radiation Research · doi:10.1667/rr3140 · Cited by 190 · see citing works
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Break-induced replication: functions and molecular mechanism
Malkova, A., & Ira, G. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.05.007 · Cited by 180 · see citing works
Yang, N.-J., Galick, H., & Wallace, S. (2004) · DNA Repair · doi:10.1016/j.dnarep.2004.04.014 · Cited by 175 · see citing works
Chromosomes without a 30-nm chromatin fiber
Joti, Y., Hikima, T., Nishino, Y., Kamada, F., Hihara, S., Takata, H., Ishikawa, T., & Maeshima, K. (2012) · Nucleus · doi:10.4161/nucl.21222 · Cited by 172 · cited 1× · see citing works
“…of higher order chromatin would take us beyond the scope of this review, but interested readers may wish to consult one or more of the recent reviews of the subject (van Holde and Zlatanova, 2007; Tremethick, 2007; Mozziconacci and Lavelle, 2009; Grigoryev and Woodcock, 2012; Joti et al., 2012).”
BackgroundLinker histones H1 and H5 prevent the mobility of positioned nucleosomes.
Pennings, S., Meersseman, G., & Bradbury, E. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10275 · Cited by 171 · see citing works
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The Three-Dimensional Structure of Human Interphase Chromosomes Is Related to the Transcriptome Map
Götze, S., Langerak, J. M., Gierman, H. J., de Leeuw, W. C., Giromus, O., Indemans, M. H. G., Köster, J., Ondřej, V., Versteeg, R., & DRIEL, R. V. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00208-07 · Cited by 162 · cited 1× · see citing works
“The chromatin within these regions is in a relatively open configuration (Goetze et al., 2007).”
BackgroundChromothripsis and Human Disease: Piecing Together the Shattering Process
Maher, C. A., & Wilson, R. K. (2012) · Cell · doi:10.1016/j.cell.2012.01.006 · Cited by 159 · cited 1× · see citing works
“Other distinguishing features of chromothripsis include a low gene copy number within shattered regions, and alternations between retained heterozygosity and loss of heterozygosity (Maher and Wilson, 2012).”
Asaithamby, A., & Chen, D. J. (2010) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2010.11.002 · Cited by 156 · cited 1× · see citing works
“There are several excellent, recent reviews of DSB repair for readers looking for more detailed expositions (e.g., San Filippo et al., 2008; Lieber, 2010; Polo and Jackson, 2011; Asaithamby and Chen, 2011; Thompson, 2012; Mehta and Haber, 2014).”
BackgroundTichy, E. D., Pillai, R., Deng, L., Liang, L., Tischfield, J., Schwemberger, S. J., Babcock, G. F., & Stambrook, P. J. (2010) · Stem Cells and Development · doi:10.1089/scd.2010.0058 · Cited by 152 · see citing works
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Mutations Arising During Repair of Chromosome Breaks
Malkova, A., & Haber, J. E. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155547 · Cited by 142 · cited 13× · see citing works
“In addition to checkpoint control-related mechanisms, the choice of HRR over NHEJ in S and G2 phases is influenced by the cell cycle-dependent, activating phosphorylation of the resection factor Sae2 (Huertas et al., 2008).”
BackgroundInfluentialChromatin organization — The 30nm fiber
Grigoryev, S. A., & Woodcock, C. L. F. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.02.014 · Cited by 139 · cited 1× · see citing works
“…of higher order chromatin would take us beyond the scope of this review, but interested readers may wish to consult one or more of the recent reviews of the subject (van Holde and Zlatanova, 2007; Tremethick, 2007; Mozziconacci and Lavelle, 2009; Grigoryev and Woodcock, 2012; Joti et al., 2012).”
BackgroundReynolds, P., Anderson, J. A., Harper, J. V., Hill, M. A., Botchway, S. W., Parker, A. W., & O’Neill, P. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks879 · Cited by 134 · see citing works
Higher-order chromatin structure in DSB induction, repair and misrepair
Falk, M., Lukášová, E., & Kozubek, S. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2010.01.013 · Cited by 131 · cited 1× · see citing works
“A related challenge is the apparent suppression of g-H2AX foci formation in heterochromatin (Kim et al., 2007) and the correspondingly slow repairofDSBs in heterochromatin (Slijepcevic andNatarajan, 1994; reviewed in Falk et al., 2010).”
BackgroundActivation of DSB Processing Requires Phosphorylation of CtIP by ATR
Peterson, S., Li, Y., Wu-Baer, F., Chait, B. T., Baer, R. J., Yan, H., Gottesman, M. E., & Gautier, J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.11.020 · Cited by 131 · see citing works
Complex regulation and function of activation-induced cytidine deaminase
Stavnezer, J. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.03.003 · Cited by 130 · see citing works
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“…30-40 nm (reflecting side-by-side packing of 30 nm chromatin filaments), 11 and 6 nm (reflecting the packing constraints of individual nucleosomes), and 2.1 and 2.7 nm (reflecting thediameter ofDNAand its pitchwithin nucleosomes, respectively) (Langmore and Paulson, 1983, and references therein).”
BackgroundInfluential32. E. Heitz: Heterochromatin, Chromocentren, Chromomeren
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Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age
Vaidya, A. M., Mao, Z., Tian, X., Spencer, B., Seluanov, A., & Gorbunova, V. A. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004511 · Cited by 119 · see citing works
Yang, N., Chaudhry, M. A., & Wallace, S. S. (2005) · DNA repair · doi:10.1016/j.dnarep.2005.07.003 · Cited by 119 · cited 1× · see citing works
“There is compelling evidence that BER-driven DSB formation also occurs in vivo, in both prokaryotes and eukaryotes (Blaisdell andWallace, 2001; Blaisdell et al., 2001; Yang et al., 2004; Yang et al., 2006).”
BackgroundBase Excision Repair Processing of Radiation-induced Clustered DNA Lesions
Blaisdell, J. O., Harrison, L., & Wallace, S. S. (2001) · Radiation Protection Dosimetry · doi:10.1093/oxfordjournals.rpd.a006634 · Cited by 119 · cited 1× · see citing works
“There is compelling evidence that BER-driven DSB formation also occurs in vivo, in both prokaryotes and eukaryotes (Blaisdell andWallace, 2001; Blaisdell et al., 2001; Yang et al., 2004; Yang et al., 2006).”
BackgroundDahm-Daphi, C. S. J. (2000) · International Journal of Radiation Biology · doi:10.1080/095530000139023 · Cited by 115 · cited 3× · see citing works
“Ye Y, Stahley MR, Xu J, Friedman JI, Sun Y, McKnight JN, Gray JJ, Bowman GD, Stivers JT. 2012.”
BackgroundCancer Genomes Evolve by Pulverizing Single Chromosomes
Meyerson, M., & Pellman, D. (2011) · Cell · doi:10.1016/j.cell.2010.12.025 · Cited by 115 · see citing works
Rydberg, B., Holley, W. R., Mian, S. I., & Chatterjee, A. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2150 · Cited by 114 · see citing works
Rules of engagement for base excision repair in chromatin
Odell, I. D., Wallace, S. S., & Pederson, D. S. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24134 · Cited by 113 · see citing works
Self-citationHypersensitivity of DNA in transcriptionally active chromatin to ionizing radiation
Chiu, S., Oleinick, N. L., Friedman, L. R., & Stambrook, P. J. (1982) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(82)90166-x · Cited by 104 · cited 1× · see citing works
“By combining pulsed field gel electrophoresis with Southern blotting, (Chiu et al., 1982) were able to show that housekeeping genes aremore vulnerable to IR-inducedDSBs thana-satelliteorbulkDNA.”
MethodSystematic Review: Charged-Particle Radiation Therapy for Cancer
Terasawa, T., Dvorak, T., Ip, S., Raman, G., Lau, J., & Trikalinos, T. A. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-151-8-200910200-00145 · Cited by 104 · see citing works
Colnaghi, R., Carpenter, G., Volker, M., & O’Driscoll, M. (2011) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.07.010 · Cited by 98 · cited 1× · see citing works
“This sets the stage for another round of NHEJ that restores the dicentric chromosome, allowing the breakage-fusion cycle to repeat (Colnaghi et al., 2011; Meyerson and Pellman, 2011).”
BackgroundWeinfeld, M., & Soderlind, K. J. M. (1991) · Biochemistry · doi:10.1021/bi00218a031 · Cited by 98 · see citing works
Rodriguez, Y., & Smerdon, M. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.441444 · Cited by 98 · see citing works
Chromatin fiber structure: Where is the problem now?
van Holde, K., & Zlatanova, J. S. (2007) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2007.08.005 · Cited by 97 · see citing works
Polyamine-nucleic acid interactions and the effects on structure in oriented DNA fibers
van Dam, L. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.2.419 · Cited by 97 · see citing works
Heterochromatin and chromosome aberrations
Natarajan, A. T., & Ahnstr�m, G. (1969) · Chromosoma · doi:10.1007/bf00325989 · Cited by 91 · see citing works
The complexity of DNA double strand breaks is a critical factor enhancing end-resection
Yajima, H., Fujisawa, H., Nakajima, N. I., Hirakawa, H., Jeggo, P. A., Okayasu, R., & Fujimori, A. (2013) · DNA repair · doi:10.1016/j.dnarep.2013.08.009 · Cited by 90 · see citing works
Galactic cosmic ray composition and energy spectra
Mewaldt, R. A. (1994) · Advances in Space Research · doi:10.1016/0273-1177(94)90536-3 · Cited by 88 · cited 1× · see citing works
“The remaining 1% are high-Z, high-energy (HZE) atomic nuclei, derived from heavier elements (Mewaldt, 1994; NASA, 2006).”
BackgroundDNA end resection is needed for the repair of complex lesions in G1-phase human cells
Averbeck, N., Ringel, O., Herrlitz, M., Jakob, B., Durante, M., & Taucher-Scholz, G. (2014) · Cell Cycle · doi:10.4161/15384101.2015.941743 · Cited by 88 · cited 1× · see citing works
“It appears, however, that CtIP and other end resection factors can be recruited to complexDSBs in G1 phase (Yajima et al., 2013; Averbeck et al., 2014) where, presumably, they initiate MMEJ-mediated repair of complex damages.”
BackgroundRadioprotection of DNA by Polyamines
Spotheim-Maurizot, M., Ruiz, S., Sabattier, R., & Charlier, M. (1995) · International Journal of Radiation Biology · doi:10.1080/09553009514551561 · Cited by 88 · see citing works
When catastrophe strikes a cell
Tubío, J. M. C., & Estivill, X. (2011) · Nature · doi:10.1038/470476a · Cited by 88 · see citing works
Franchet-Beuzit, J., Spotheim-Maurizot, M., Sabattier, R., Blazy, B., & Charlier, M. (1993) · Biochemistry · doi:10.1021/bi00059a031 · Cited by 87 · cited 2× · see citing works
“Variations in groove width are sometimes sequence-directed, which may, for example, explain why 5’-AATT-3’ sequences are less sensitive than average to radiation-induced strand-breaks (Franchet-Beuzit et al., 1993; Sy JOURNAL OF CELLULAR PHYSIOLOGY et al., 1997).”
BackgroundDuharcourt, S., Lepère, G., & Meyer, É. (2009) · Trends in Genetics · doi:10.1016/j.tig.2009.05.007 · Cited by 85 · cited 1× · see citing works
“Programmed formation of DSBs also occurs during the development of somatic nuclei in protozoans (reviewed in Duharcourt et al., 2009), mating-type switching in yeast (reviewed in Haber, 2012), T-cell receptor formation in T-lymphocytes, and immunoglobulin class switching in B-lymphocytes (reviewed…”
BackgroundSutherland, B. M., Georgakilas, A. G., Bennett, P. V., Laval, J., & Sutherland, J. C. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.005 · Cited by 85 · see citing works
Zhou, T., Akopiants, K., Mohapatra, S., Lin, P.-S., Valerie, K. C., Ramsden, D. A., Lees‐Miller, S. P., & Povirk, L. F. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.05.003 · Cited by 84 · cited 1× · see citing works
“Tyrosyl-DNA phosphodiesterase, for example, can require several hours to remove phosphoglycolate moieties from 3’ DNA ends (Zhou et al., 2009).”
BackgroundThe shape of the radiation dose response for DNA double-strand break induction and repair
Barnard, S. G. R., Bouffler, S. D., & Rothkamm, K. (2013) · Genome Integrity · doi:10.1186/2041-9414-4-1 · Cited by 83 · see citing works
Prasad, A., Wallace, S. S., & Pederson, D. S. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00791-07 · Cited by 83 · see citing works
Self-citationBase excision repair of 8-oxoG in dinucleosomes
Menoni, H., Shukla, M. S., Gerson, V., Dimitrov, S. I., & Angelov, D. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr761 · Cited by 81 · cited 1× · see citing works
“…lesions are repaired varies bothwith the distance between the lesion and the edge of the nucleosome, and the lesion’s helical orientation relative to the underlying histoneoctamer (Odell et al., 2013; also, Menoni et al., 2012; Ye et al., 2012; Maher et al., 2013; Rodriguez and Smerdon, 2013).”
BackgroundTakahashi, T. S., Burguiere-Slezak, G., van der Kemp, P. A., & Boiteux, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012582108 · Cited by 77 · see citing works
Lorat, Y., Schanz, S., Schuler, N., Wennemuth, G., Rübe, C., & Rübe, C. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038165 · Cited by 70 · cited 1× · see citing works
“Indeed, DSB repair may not occur at all until heterochromatin decondenses (Kruhlak et al., 2006; Lorat et al., 2012).”
BackgroundEstimation of Yields of OH Radicals in Water Irradiated by Ionizing Radiation
Yamaguchi, H., Uchihori, Y., YASUDA, N., Takada, M., & Kitamura, H. (2005) · Journal of Radiation Research · doi:10.1269/jrr.46.333 · Cited by 70 · see citing works
Sequence-dependent variations of DNA structure modulate radiation-induced strand breakage
D. SY, C. S. (1997) · International Journal of Radiation Biology · doi:10.1080/095530097143365 · Cited by 70 · see citing works
Cannan, W. J., Tsang, B. P., Wallace, S. S., & Pederson, D. S. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.571588 · Cited by 68 · cited 1× · see citing works
“When tested however, nucleosomes suppressed DSB formation at clustered lesions far more than predicted (Cannan et al., 2014).”
BackgroundSelf-citationChromatin structure and radiation-induced DNA damage: From structural biology to radiobiology
Lavelle, C., & Foray, N. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.01.012 · Cited by 68 · cited 1× · see citing works
“Evidence of this includes studies in which the frequency of DSB formation increased after chromatin-associated proteins were stripped from DNA, using high salt (reviewed in Lavelle and Foray, 2014).”
BackgroundRadiation-induced DNA Damage and Chromatin Structure
Rydberg, B. (2001) · Acta Oncologica · doi:10.1080/02841860152619070 · Cited by 66 · see citing works
Radulescu, I., Elmroth, K., & Stenerlöw, B. (2004) · Radiation Research · doi:10.1667/rr3094 · Cited by 65 · see citing works
The relation between the unit thread of chromosomes and isolated nucleohistone
Pooley, A. S., Pardon, J. F., & Richards, B. M. (1974) · Journal of Molecular Biology · doi:10.1016/0022-2836(74)90314-3 · Cited by 64 · see citing works
The radiation hypersensitivity of cells at mitosis
Stobbe, C. C., Park, S. J., & Chapman, J. D. (2002) · International Journal of Radiation Biology · doi:10.1080/09553000210166570 · Cited by 64 · see citing works
Frankenberg-Schwager, M., Gebauer, A., Koppe, C., Wolf, H., Pralle, E., & Frankenberg, D. (2009) · Radiation Research · doi:10.1667/rr0784.1 · Cited by 63 · cited 1× · see citing works
“This creates a substrate that, following removal of non-annealed DNA ends, is competent for gap filling and ligation (by DNA ligase IV in yeast and DNA ligase III in mammalian cells), as also occurs during single strand annealing repair (see Frankenberg-Schwager et al., 2009).”
BackgroundRecombination and ReplicationPreprint
Syeda, A. H., Hawkins, M., & McGlynn, P. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016550 · Cited by 62 · see citing works
Pinto, M., Prise, K. M., & Michael, B. D. (2005) · Radiation Research · doi:10.1667/rr3394 · Cited by 61 · see citing works
Modeling of ultrasoft X-ray induced DNA damage using structured higher order DNA targets
Bernhardt, P., Friedland, W., Jacob, P., & Paretzke, H. G. (2002) · International Journal of Mass Spectrometry · doi:10.1016/s1387-3806(02)00879-5 · Cited by 57 · cited 1× · see citing works
“It also supports the use of IR-induced DSB patterns to determine nucleosome positions and investigate the structure of the 30 nm chromatin fiber (Rydberg et al., 1998; Rydberg, 2001; Bernhardt et al., 2003).”
MethodDNA interstrand cross-links induced by ionizing radiation: An unsung lesion
Dextraze, M.-E., Gantchev, T. G., Girouard, S., & Hunting, D. J. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2009.12.007 · Cited by 56 · cited 1× · see citing works
“…structures, bulky lesions, polymerase blocking oxidative lesions, abasic sites, chemical or IR-generated inter-strand crosslinks, or as a result of collisions with transcription complexes and certain DNA binding proteins (Prado and Aguilera, 2005; Mirkin and Mirkin, 2007; Dextraze et al., 2010).”
BackgroundStereo electron microscopy of the 25-nm chromatin fibers in isolated nuclei.
Olins, A. L., & Olins, D. E. (1979) · The Journal of Cell Biology · doi:10.1083/jcb.81.1.260 · Cited by 56 · see citing works
Enzymatic Excision of Uracil Residues in Nucleosomes Depends on the Local DNA Structure and Dynamics
Ye, Y., Stahley, M. R., Xu, J., Friedman, J. I., Sun, Y., McKnight, J. N., Gray, J. J., Bowman, G. D., & Stivers, J. T. (2012) · Biochemistry · doi:10.1021/bi3006412 · Cited by 55 · see citing works
Energy deposition mechanisms and biochemical aspects of DNA strand breaks by ionizing radiation
Chatterjee, A., & Holley, W. R. (1991) · International Journal of Quantum Chemistry · doi:10.1002/qua.560390508 · Cited by 53 · cited 1× · see citing works
“Although low LET IR can create closely-spaced, clustered lesions (Chatterjee and Holley, 1991), collisions between low LET particles and atoms in tissues are infrequent, and thus low to moderate levels of low-LET may produce DSBs that are more or less randomly distributed.”
BackgroundSlijepčević, P., & Natarajan, A. T. (1994) · Mutation Research Letters · doi:10.1016/0165-7992(94)90084-1 · Cited by 53 · see citing works
Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles
Staaf, E., Brehwens, K., Haghdoost, S., Czub, J., & Wójcik, A. (2012) · Genome Integrity · doi:10.1186/2041-9414-3-8 · Cited by 52 · cited 1× · see citing works
“(Staaf et al., 2012) reported that gamma (photon) radiation generates as many or more g-H2AX-marked DSB repair foci than doa particles.”
BackgroundWarters, R. L., Newton, G. L., Olive, P. L., & Fahey, R. C. (1999) · Radiation Research · doi:10.2307/3579948 · Cited by 50 · see citing works
Folle, G. A., Martínez‐López, W., Boccardo, E., & Obe, G. (1998) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(98)00090-6 · Cited by 48 · cited 1× · see citing works
“However, later studies indicated that translocations occur more frequently in euchromatin (reviewed in Folle et al., 1998).”
BackgroundChiu, S., & Oleinick, N. L. (1998) · Radiation Research · doi:10.2307/3579900 · Cited by 48 · cited 1× · see citing works
“Aswell, small molecules, such as the polyamine spermine, can moderate reactions between ROS and DNA (Spotheim-Maurizot et al., 1995; Chiu and Oleinick, 1998; Warters et al., 1999).”
BackgroundPeriodicity of exonuclease III digestion of chromatin and the pitch of DNA on the nucleosome
Prunell, A. (1983) · Biochemistry · doi:10.1021/bi00290a004 · Cited by 40 · see citing works
Point/Counterpoint: Low-dose radiation is beneficial, not harmful
Doss, M., Little, M. P., & Orton, C. G. (2014) · Medical Physics · doi:10.1118/1.4881095 · Cited by 39 · cited 1× · see citing works
“There is much less agreement on the risks associated with very low dose IR (e.g., Doss et al., 2014).”
BackgroundSung, W., Park, J. M., Choi, C. H., Ha, S. W., & Ye, S. (2012) · Radiation Oncology Journal · doi:10.3857/roj.2012.30.1.27 · Cited by 36 · see citing works
Radiation-induced Damages in Single- and Double-stranded DNA
Isabelle, V., Prévost, C., Spotheim-Maurizot, M., Sabattier, R., & Charlier, M. (1995) · International Journal of Radiation Biology · doi:10.1080/09553009514550211 · Cited by 36 · cited 1× · see citing works
“As summarized in Table 2, those atoms are less accessible in DNA with unusually narrow minor grooves (Isabelle et al., 1995).”
BackgroundMaher, R. L., Prasad, A., Rizvanova, O., Wallace, S. S., & Pederson, D. S. (2013) · DNA repair · doi:10.1016/j.dnarep.2013.08.010 · Cited by 34 · cited 2× · see citing works
“…lesions are repaired varies bothwith the distance between the lesion and the edge of the nucleosome, and the lesion’s helical orientation relative to the underlying histoneoctamer (Odell et al., 2013; also, Menoni et al., 2012; Ye et al., 2012; Maher et al., 2013; Rodriguez and Smerdon, 2013).”
BackgroundSelf-citationComputational biology : new research
Russe, A. S. (2009) · Nova Science Publishers eBooks · Cited by 25 · see citing works
Bunch, R. T., Gewirtz, D. A., & Povirk, L. F. (1995) · International Journal of Radiation Biology · doi:10.1080/09553009514551541 · Cited by 25 · cited 1× · see citing works
“Aswell, active genes were often found to occur in clusters, surrounded by more radiosensitive chromatin (Bunch et al., 1995).”
BackgroundConsequences and Repair of Oxidative DNA Damage
Duclos, S., Doublié, S., & Wallace, S. S. (2012) · Issues in toxicology · doi:10.1039/9781849732925-00115 · Cited by 22 · cited 1× · see citing works
“Most such lesions are subject to base excision repair (BER), which entails production of gapped repair intermediates (for reviews, see David et al., 2007; Hegde et al., 2008; Robertson et al., 2009; Duclos et al., 2012; Krokan and Bjoras, 2013; Wallace, 2014).”
BackgroundChromatin Compaction and Tumor Cell Radiosensitivity at 2 Gray
Chapman, J. D., Stobbe, C. C., & Matsumoto, Y. (2001) · American Journal of Clinical Oncology · doi:10.1097/00000421-200110000-00019 · Cited by 14 · cited 1× · see citing works
“Thus, slow or delayed repair could explain reports of elevated radiation sensitivity in condensed chromatin (Chapman et al., 2001; Stobbeet al., 2002).”
BackgroundNeutron and Gamma-Radiation Sensitivity of Plasmid DNA of Varying Superhelical Density
Swenberg, C. E., & Speicher, J. M. (1995) · Radiation Research · doi:10.2307/3578950 · Cited by 10 · see citing works
Modulation of Enediyne-Induced DNA Damage by Chromatin Structures in Transcriptionally Active Genes
Wu, J., Xu, J. J., & Dedon, P. C. (1999) · Biochemistry · doi:10.1021/bi991999+ · Cited by 8 · see citing works
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Inflammation-induced DNA damage, mutations and cancer
Kay, J. E., Thadhani, E., Samson, L. D., & Engelward, B. P. (2019) · DNA repair · doi:10.1016/j.dnarep.2019.102673 · Cited by 481 · see citing works
Advances in genome editing through control of DNA repair pathways
Yeh, C. D., Richardson, C. D., & Corn, J. E. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0425-z · Cited by 405 · see citing works
DNA Damage/Repair Management in Cancers
Alhmoud, J. F., Woolley, J. F., Moustafa, A. A., & Malki, M. I. (2020) · Cancers · doi:10.3390/cancers12041050 · Cited by 378 · see citing works
“Genotoxic agents cause structural changes in DNA by disrupting covalent bonds between nucleotides, preventing accurate replication of the genome [3].”
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Karagöz, G. E., Acosta‐Alvear, D., & Walter, P. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033886 · Cited by 302 · see citing works
Hyperthermia: The Optimal Treatment to Overcome Radiation Resistant Hypoxia
Elming, P. B., Sørensen, B. S., Oei, A. L., Franken, N. A. P., Crezee, J., Overgaard, J., & Horsman, M. R. (2019) · Cancers · doi:10.3390/cancers11010060 · Cited by 206 · see citing works
“Ionizing radiation causes different DNA lesions that include base damage, single strand breaks (SSBs) and double strand breaks (DSBs), the latter being produced either directly by an ionizing event or indirectly when SSBs are produced close to each other on both DNA strands [51] or indirectly when problems occur durin…”
BackgroundBRCA-related ATM-mediated DNA double-strand break repair and ovarian aging
Turan, V., & Oktay, K. (2019) · Human Reproduction Update · doi:10.1093/humupd/dmz043 · Cited by 178 · see citing works
Potential of Copper and Copper Compounds for Anticancer Applications
Ji, P., Wang, P., Chen, H., Xu, Y., Ge, J., Tian, Z., & Yan, Z. (2023) · Pharmaceuticals · doi:10.3390/ph16020234 · Cited by 171 · see citing works
“Induced DNA damage MKN-45 and BGC-823 cells Inducing DSBs leads to cancer cell death [60]”
BackgroundUpdate of the risk assessment of inorganic arsenic in food
(CONTAM), E. P. O. C. I. T. F. C., Schrenk, D., Bignami, M., Bodin, L., Chipman, J. K., del Mazo, J., Grasl‐Kraupp, B., Högstrand, C., Hoogenboom, L. A. P., Leblanc, J., et al. (2024) · EFSA Journal · doi:10.2903/j.efsa.2024.8488 · Cited by 156 · see citing works
Atherosclerosis Is a Smooth Muscle Cell–Driven Tumor-Like Disease
Pan, H., Ho, S. E., Xue, C., Cui, J. G., Johanson, Q., Sachs, N., Ross, L. S., Li, F., Solomon, R. A., Connolly, E. S., et al. (2024) · Circulation · doi:10.1161/circulationaha.123.067587 · Cited by 153 · see citing works
“20 Indeed, estimation of tailed nuclei in the comet assay 21 revealed extensive single-/double-strand DNA breaks in SMC lineage cells (including ZsGreen1 + SMCs and SDCs) pooled from advanced atherosclerosis but very few in SMCs from healthy mouse aortas (Figure 1D).”
BackgroundCasanovas, A., Ribas‐Maynou, J., Lara-Cerrillo, S., Jimenez-Macedo, A. R., Hortal, O., Benet, J., Carrera, J., & García-Peiró, A. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.11.035 · Cited by 134 · see citing works
Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases
Shadfar, S., Parakh, S., Jamali, M. S., & Atkin, J. D. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00350-4 · Cited by 135 · see citing works
“DSBs can also be produced following adjacent sites damaged by IR that are present on both DNA strands [82].”
BackgroundMechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease
Welch, G., & Tsai, L. (2022) · The EMBO Reports · doi:10.15252/embr.202154217 · Cited by 129 · see citing works
“…with the transcriptional machinery and replication forks, or through their close proximity to another SSB. DSBs are also directly generated by transcription (Cannan & Pederson, 2016), whereby topoisomerase II (TOP2) induces transient DSBs to relieve torsional stress and facilitate gene expression.”
Płuciennik, K., Sicińska, P., Misztal, W., & Bukowska, B. (2024) · Cells · doi:10.3390/cells13090768 · Cited by 127 · see citing works
“Damage to DNA also proceeds as a result of action of exogenous factors, such as various chemicals [76,77].”
BackgroundMitochondria and mitochondrial DNA as relevant targets for environmental contaminants
Roubicek, D. A., & de Souza-Pinto, N. C. (2017) · Toxicology · doi:10.1016/j.tox.2017.06.012 · Cited by 122 · see citing works
Plasticity of the Mre11–Rad50–Xrs2–Sae2 nuclease ensemble in the processing of DNA-bound obstaclesPreprint
Wang, W., Daley, J. M., Kwon, Y., Krasner, D. S., & Sung, P. (2017) · Genes & Development · doi:10.1101/gad.307900.117 · Cited by 117 · see citing works
“DNA double-strand breaks (DSBs) are induced by ionizing radiation (IR) and chemotherapeutic drugs and can also arise from DNA replication fork stalling or collapse (Petermann et al. 2010; Pommier et al. 2010; Cannan and Pederson 2016).”
BackgroundThe Enterobacterial Genotoxins: Cytolethal Distending Toxin and Colibactin
Taieb, F. E., Petit, C. R., Nougayrède, J., & Oswald, É. (2016) · EcoSal Plus · doi:10.1128/ecosalplus.esp-0008-2016 · Cited by 113 · see citing works
“To deal with this DNA injury, cells have evolved sophisticated mechanisms to repair DNA damage such as DNA breaks, DNA adducts and cross-links, and to resolve replication fork-dependent DNA breaks during replication and transcription (7).”
BackgroundGenotoxic therapy and resistance mechanism in gliomas
Lang, F., Liu, Y., Chou, F.-J., & Yang, C. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107922 · Cited by 113 · see citing works
CRISPR-Based Gene Therapies: From Preclinical to Clinical Treatments
Laurent, M., Geoffroy, M., Pavani, G., & Guiraud, S. (2024) · Cells · doi:10.3390/cells13100800 · Cited by 122 · see citing works
Acquired genetic changes in human pluripotent stem cells: origins and consequences
Halliwell, J. A., Barbaric, I., & Andrews, P. W. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00292-z · Cited by 101 · see citing works
Targeting CDK12 for Cancer Therapy: Function, Mechanism, and Drug Discovery
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DNA Damage-Inducing Anticancer Therapies: From Global to Precision Damage
Reuvers, T. G. A., Kanaar, R., & Nonnekens, J. (2020) · Cancers · doi:10.3390/cancers12082098 · Cited by 103 · see citing works
“DSBs are a detrimental form of DNA damage, as even a single DSB is capable of inducing cell death, and their induction and processing can be highly mutagenic and have far-reaching consequences for the genome [11,12].”
BackgroundUnboxing the molecular modalities of mutagens in cancer
Kumari, S., Sharma, S., Advani, D., Khosla, A., Kumar, P., & Ambasta, R. K. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-16726-w · Cited by 105 · see citing works
“The polymerization is carried out by DNA polymerase θ (Polθ), while the DNA ligase III -XRCC1 complex is required for the final ligation step (Cannan and Pederson 2016).”
BackgroundMajor Molecular Signaling Pathways in Oral Cancer Associated With Therapeutic Resistance
Usman, S., Jamal, A., Teh, M., & Waseem, A. (2021) · Frontiers in Oral Health · doi:10.3389/froh.2020.603160 · Cited by 91 · see citing works
“Three possible pathways repair DSBs; 1, nonhomologous end joining (NHEJ), 2, microhomology-mediated end joining (MMEJ); and 3, homologous recombination (HR) [164].”
BackgroundMahapatra, K., De, S., Banerjee, S., & Roy, S. (2019) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2019.02.056 · Cited by 93 · see citing works
RetractedIn trans paired nicking triggers seamless genome editing without double-stranded DNA cutting
Chen, X., Janssen, J. M., Liu, J., Maggio, I., Jong, A. E. J. ‘., Mikkers, H. M. M., & Gonçalves, M. A. F. V. (2017) · Nature Communications · doi:10.1038/s41467-017-00687-1 · Cited by 92 · see citing works
Penninckx, S., Pariset, E., Cekanaviciute, E., & Costes, S. V. (2021) · NAR Cancer · doi:10.1093/narcan/zcab046 · Cited by 90 · see citing works
RNase H eliminates R‐loops that disrupt DNA replication but is nonessential for efficient DSB repair
Zhao, H., Zhu, M., Limbo, O., & Russell, P. R. (2018) · EMBO Reports · doi:10.15252/embr.201745335 · Cited by 86 · see citing works
“To more directly explore the role of RNase H in DSB repair, we performed survival assays using IR emitted from a cesium-137 source [32,33].”
Grundy, G. J., Rulten, S. L., Arribas-Bosacoma, R., Davidson, K., Kozik, Z., Oliver, A. W., Pearl, L. H., & Caldecott, K. W. (2016) · Nature Communications · doi:10.1038/ncomms11242 · Cited by 84 · see citing works
“Intriguingly, database searches using Pattinprot and the core minimal KBM sequence (R-X-X-P-X-W) identified more than 600 proteins with this motif (Supplementary Data 1).”
Westphalen, C. B., Fine, A. D., André, F., Ganesan, S., Heinemann, V., Rouleau, É., Turnbull, C., Palacios, L. G., López, J. A., Sokol, E. S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2096 · Cited by 77 · see citing works
“In the absence of functional HRR, non-homologous end joining, microhomology-mediated end joining, and single-strand annealing are used to repair double-stranded breaks (12).”
Metastatic Castration-Resistant Prostate Cancer: Advances in Treatment and Symptom Management
Kulasegaran, T., & Oliveira, N. (2024) · Current Treatment Options in Oncology · doi:10.1007/s11864-024-01215-2 · Cited by 81 · see citing works
“This process is called homologous recombination repair (HRR), which accurately repairs double-strand breaks during the synthesis (S) and Gap 2 (G2) phases of the cell cycle [30].”
BackgroundLee, C. Y., O’Connell, C. D., Onofrillo, C., Choong, P., Bella, C. D., & Duchi, S. (2019) · Stem Cells Translational Medicine · doi:10.1002/sctm.19-0192 · Cited by 70 · see citing works
“When two closely opposed single strand breaks, commonly referred to as “clustered damages,” form, the molecule cannot be resealed thus converts into a DSBs.74 In addition to breaks, repair of other clustered DNA lesions by simultaneous base excision repair can result in single strand breaks which can convert to DSBs.7…”
BackgroundCRISPR Variants for Gene Editing in Plants: Biosafety Risks and Future Directions
Movahedi, A., Dargiri, S. A., Li, H., Zhuge, Q., & Sun, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216241 · Cited by 79 · see citing works
“These forms of radiation induce structural changes in the DNA, such as double-strand breaks and chromosomal rearrangements in cells [17].”
BackgroundStress-Induced Mutagenesis, Gambler Cells, and Stealth Targeting Antibiotic-Induced Evolution
Pribis, J. P., Zhai, Y., Hastings, P. J., & Rosenberg, S. M. (2022) · mBio · doi:10.1128/mbio.01074-22 · Cited by 69 · see citing works
van de Kooij, B., Kruswick, A., van Attikum, H., & Yaffe, M. B. (2022) · Nature Communications · doi:10.1038/s41467-022-32743-w · Cited by 69 · see citing works
“Each panel shows, from top to bottom (1) the fluorescence changes caused by repair of the site-specific DSB in the depicted”
BackgroundDNA Damage Responses during the Cell Cycle: Insights from Model Organisms and Beyond
Clay, D. E., & Fox, D. T. (2021) · Genes · doi:10.3390/genes12121882 · Cited by 68 · see citing works
“DSBs are deleterious in nature as they can lead to loss of large amounts of genetic material during cell divisions if not responded to properly [3,45].”
BackgroundOrganophosphate pesticide-induced toxicity through DNA damage and DNA repair mechanisms
Prathiksha, J., Narasimhamurthy, R. K., Dsouza, H. S., & Mumbrekar, K. D. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08424-2 · Cited by 68 · see citing works
The genomic landscape of 8-oxodG reveals enrichment at specific inherently fragile promoters
Gorini, F., Scala, G., Di Palo, G., Dellino, G. I., Cocozza, S., Pelicci, P. G., Lania, L., Majello, B., & Amente, S. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa175 · Cited by 67 · see citing works
Alkhalifa, A. E., Alkhalifa, O., Durdanovic, I., Ibrahim, D. R., & Maragkou, S. (2025) · Journal of Dementia and Alzheimer's Disease · doi:10.3390/jdad2020017 · Cited by 66 · see citing works
Profiling DNA break sites and transcriptional changes in response to contextual fear learning
Stott, R. T., Kritsky, O., & Tsai, L.-H. (2021) · PLOS ONE · doi:10.1371/journal.pone.0249691 · Cited by 62 · see citing works
“Additionally, two closely spaced single-strand DNA breaks (SSBs) could potentially be recognized as a DSB by the cell [71].”
BackgroundStrategies for the Nuclear Delivery of Metal Complexes to Cancer Cells
Huynh, M., Vinck, R., Gibert, B., & Gasser, G. (2024) · Advanced Materials · doi:10.1002/adma.202311437 · Cited by 59 · see citing works
Synthetic Lethality through the Lens of Medicinal Chemistry
Myers, S. H., Ortega, J. A., & Cavalli, A. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00766 · Cited by 60 · see citing works
Genome-wide analysis of DNA replication and DNA double-strand breaks using TrAEL-seq
Kara, N., Krueger, F., Rugg‐Gunn, P. J., & Houseley, J. M. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3000886 · Cited by 55 · see citing works
Molecular Spectroscopic Markers of DNA Damage
Sofińska, K., Wilkosz, N., Szymoński, M., & Lipiec, E. W. (2020) · Molecules · doi:10.3390/molecules25030561 · Cited by 55 · see citing works
“The BER pathway is mainly activated in response to factors like oxidation, hydrolytic deamination, alkylation, ionizing radiation, intracellular metabolites, or ROS due to UV radiation [18,19].”
BackgroundThe Complex Mechanisms by Which Neurons Die Following DNA Damage in Neurodegenerative Diseases
Shadfar, S., Brocardo, M. G., & Atkin, J. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052484 · Cited by 54 · see citing works
“DSBs are also known to induce FUS phosphorylation via DNA-PK and ATM [292,293].”
BackgroundInfluentialBouwman, B. A. M., & Crosetto, N. (2018) · Genes · doi:10.3390/genes9120632 · Cited by 53 · see citing works
“While exogenous genotoxic insults contribute to this [7,8], in healthy individuals the majority of DSBs is thought to originate from within the nucleus, where DSBs form during fundamental processes such as DNA replication, meiosis, antibody diversification, gene transcription, and—although indirectly—cellular metaboli…”
BackgroundAli, M. K., Shahin, S. M., Sabri, N. A., Al-Hendy, A. A., & Yang, Q. (2018) · Acta Pharmacologica Sinica · doi:10.1038/s41401-018-0184-6 · Cited by 53 · see citing works
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“As a result of exposure to either exogenous or endogenous environmental stressors, DNA double-strand breaks (DSBs) abrasions occur in both DNA strands, damaging them [36].”
BackgroundDNA damage and repair following traumatic brain injury
Davis, C. K., & Vemuganti, R. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105143 · Cited by 49 · see citing works
“In most instances, adjacent single-strand breaks (SSBs) lead to double-strand breaks (DSBs) (Cannan and Pederson, 2016).”
Cho, E., Allemang, A., Audebert, M., Chauhan, V., Dertinger, S. D., Hendriks, G., Luijten, M., Marchetti, F., Minocherhomji, S., Pfuhler, S., et al. (2022) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22479 · Cited by 48 · see citing works
“Some studies suggest that multiple DNA lesions within one or two helical turns can increase the rate of DSB formation (Cannan & Pederson, 2016).”
BackgroundDNA double-strand breaks: a potential therapeutic target for neurodegenerative diseases
Thadathil, N., Hori, R. T., Xiao, J., & Khan, M. M. (2019) · Chromosome Research · doi:10.1007/s10577-019-09617-x · Cited by 48 · see citing works
The biomedical potential of tardigrade proteins: A review
Kasianchuk, N., Rzymski, P., & Kaczmarek, Ł. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114063 · Cited by 50 · see citing works
DNA double-strand break repair: a tale of pathway choices
Li, J., & Xu, X. (2016) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmw045 · Cited by 46 · see citing works
“NHEJ involves blunt-end ligation independent of sequence homology by the canonical DNA-PKcs/Ku70/80 complex.”
BackgroundInfluentialDNA damage interactions on both nanometer and micrometer scale determine overall cellular damage
Friedrich, T., Ilicic, K., Greubel, C., Girst, S., Reindl, J., Sammer, M., Schwarz, B., Siebenwirth, C., Walsh, D. W. M., Schmid, T. E., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-34323-9 · Cited by 47 · see citing works
Nucleosomes effectively shield DNA from radiation damage in living cells
Brambilla, F., García-Manteiga, J. M., Monteleone, E., Hoelzen, L., Zocchi, A., Agresti, A., & Bianchi, M. E. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa613 · Cited by 47 · see citing works
“Among ROS-induced DNA damages, single strand breaks (SSBs) and double strand breaks (DSBs) are prominent, with a much larger amount of IR-induced SSBs relative to DSBs (5); in fact, most DSBs are the outcome of two close SSBs on opposite strands of DNA (6).”
BackgroundSangermano, F., Delicato, A., & Calabrò, V. (2020) · Biochimie · doi:10.1016/j.biochi.2020.10.004 · Cited by 46 · see citing works
Ludovici, G. M., de Souza, S. O., Chierici, A., Cascone, M. G., d’Errico, F., & Malizia, A. (2020) · Journal of Environmental Radioactivity · doi:10.1016/j.jenvrad.2020.106375 · Cited by 45 · see citing works
Genome-wide detection of DNA double-strand breaks by in-suspension BLISS
Bouwman, B. A. M., Agostini, F., Garnerone, S., Petrosino, G., Gothe, H. J., Sayols, S., Moor, A. E., Itzkovitz, S., Bienko, M., Roukos, V., et al. (2020) · Nature Protocols · doi:10.1038/s41596-020-0397-2 · Cited by 43 · see citing works
Chromosome structural variation in tumorigenesis: mechanisms of formation and carcinogenesis
Wang, W., Li, L., & Cui, J. (2020) · Epigenetics & Chromatin · doi:10.1186/s13072-020-00371-7 · Cited by 44 · see citing works
“) [14, 15] Activation-induced cytidine deaminase (AID) and recombination-activating genes (RAGs) can both generate off-target DNA cleavage, thereby contributing to genomic rearrangements in cancer [16, 17].”
BackgroundLess-well known functions of cyclin/CDK complexes
Palmer, N., & Kaldis, P. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.04.003 · Cited by 43 · see citing works
Jakobsdottir, G. M., Brewer, D. S., Cooper, C., Green, C., & Wedge, D. C. (2022) · BMC Biology · doi:10.1186/s12915-022-01316-0 · Cited by 43 · see citing works
“Errors in the repair of DSBs then result in mutations, as well as causing chromosomal rearrangements [16, 22].”
BackgroundPredicting double-strand DNA breaks using epigenome marks or DNA at kilobase resolution
Mourad, R., Ginalski, K., Legube, G., & Cuvier, O. (2018) · Genome biology · doi:10.1186/s13059-018-1411-7 · Cited by 42 · see citing works
“These results reflect the importance of DNA shape in determining DSB sites, in agreement with studies showing that narrow minor grooves (created by either sequence context or DNA bending) limit access of reactive oxygen species [45].”
Single cell heterogeneity in human pluripotent stem cells
Yang, S., Cho, Y., & Jang, J. (2021) · BMB Reports · doi:10.5483/bmbrep.2021.54.10.094 · Cited by 43 · see citing works
“Errors incorporated during the DNA repair process can result in genetic abnormalities (17).”
BackgroundAtaxia 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
“12 the nuclear position of the DSBs are important [83, 86, 87].”
BackgroundSingle-Strand Annealing in Cancer
Błasiak, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042167 · Cited by 42 · see citing works
“DSBs may also result from two independent DNA single-strand breaks (SSBs) located on two DNA strands in a close vicinity–the exact distance between two SSBs to produce a DSB depends on the DNA base composition and its architecture within the nucleus [3].”
BackgroundJacczak, B., Rubiś, B., & Totoń, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126381 · Cited by 41 · see citing works
Elkafas, H., Ali, M. K., Morsy, E. M. E., Kamel, R., Thompson, W. E., Badary, O. A., Al-Hendy, A. A., & Yang, Q. (2020) · Cells · doi:10.3390/cells9061459 · Cited by 41 · see citing works
“Reports in the literature have shown that DNA damage in rapidly proliferating cells accumulates due to the inadequate expression of DNA repair genes and can increase the risk of several diseases, including cancer [44,45].”
BackgroundPARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation
Sang, C. C., Moore, G., Tereshchenko, M., Zhang, H., Nosella, M. L., Dasovich, M., Alderson, T. R., Leung, A. K. L., Finkelstein, I. J., Forman-Kay, J. D., et al. (2024) · EMBO Reports · doi:10.1038/s44319-024-00285-5 · Cited by 40 · see citing works
“Protecting and bridging broken DNA ends to keep them in close proximity would be a crucial fi rst step to ef fi cient DNA repair in multiple repair pathways (Cannan and Pederson, 2016).”
DNA Damage/Repair Management in Cancers
Alhmoud, J. F., Woolley, J. F., Moustafa, A. A., & Mallei, M. I. (2021) · doi:10.1201/9781003180449-12 · Cited by 38 · see citing works
Archaeal DNA Repair Mechanisms
Marshall, C. J., & Santangelo, T. J. (2020) · Biomolecules · doi:10.3390/biom10111472 · Cited by 40 · see citing works
Twist1 induces chromosomal instability (CIN) in colorectal cancer cells
Khot, M., Sreekumar, D., Jahagirdar, S., Kulkarni, A. M., Hari, K., Faseela, E. E., Sabarinathan, R., Jolly, M. K., & Sengupta, K. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa076 · Cited by 38 · see citing works
“Since chromosomal aberrations such as deletions are consequences of DSB formation (34,35), we sought to examine whether Twist1 overexpression induces DNA DSBs in colorectal cancer cells (Fig.”
Falk, M., & Hausmann, M. (2020) · Cancers · doi:10.3390/cancers13010018 · Cited by 39 · see citing works
“For instance, exposure to densely ionizing radiation [61,62], high or very low doses of radiation [63,64], and fractionated irradiation [65] have been recognized to increase the proportion of DSBs, whose repair is dependent on HR (Figure 1C).”
BackgroundEtoposide as a Key Therapeutic Agent in Lung Cancer: Mechanisms, Efficacy, and Emerging Strategies
Jang, J. Y., Kim, D., Im, E., & Kim, N. D. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020796 · Cited by 37 · see citing works
Ludovici, G. M., Cascone, M. G., Huber, T., Chierici, A., Gaudio, P. D., de Souza, S. O., d’Errico, F., & Malizia, A. (2021) · The European Physical Journal Plus · doi:10.1140/epjp/s13360-021-01447-3 · Cited by 37 · see citing works
The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation
Ibragimova, M., Kussainova, A., Aripova, A., Bersimbaev, R. I., & Bulgakova, O. (2024) · Cells · doi:10.3390/cells13060550 · Cited by 36 · see citing works
“The direct IR pathway involves collision of a high-energy photon with a DNA strand, which causes the phospho-diester backbone to break [171].”
BackgroundCell resistance to the Cytolethal Distending Toxin involves an association of DNA repair mechanisms
Bezine, E., Malaisé, Y., Loeuillet, A., Chevalier, M., Boutet-Robinet, E. A., Salles, B., Mirey, G., & Vignard, J. (2016) · Scientific Reports · doi:10.1038/srep36022 · Cited by 35 · see citing works
Cellular response to endogenous DNA damage: DNA base modifications in gene expression regulation
Bordin, D. L., Lirussi, L., & Nilsen, H. L. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103051 · Cited by 37 · see citing works
OECD Series on Adverse Outcome Pathways
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Telomerase and hallmarks of cancer: An intricate interplay governing cancer cell evolution
Kumar, N., & Sethi, G. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216459 · Cited by 35 · see citing works
A Survey of Reported Disease-Related Mutations in the MRE11-RAD50-NBS1 Complex
Rahman, S., Canny, M. D., Buschmann, T. A., & Latham, M. P. (2020) · Cells · doi:10.3390/cells9071678 · Cited by 35 · see citing works
“The latter includes both base alkylating chemicals, like methyl methane sulfonate (MMS), and crosslinking agents [28].”
BackgroundBRCA Mutations and Fertility Preservation
Nunes, J. D., Demeestere, I., & Devos, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010204 · Cited by 37 · see citing works
“DNA double strand breaks (DSBs) may be caused by exogenous agents (as irradiation and chemical agents such as chemotherapy) or endogenous processes (DNA replication and repair) [30,31].”
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- Authors
- Cannan, W. J., & Pederson, D. S.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Pederson, David S.
- ORCID
- Cannan, Wendy J.
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2015-09-28
- Volume
- 231
- Issue
- 1
- Pages
- 3-14
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- PMC
- PMC4994891
- OpenAlex
- W1783508367
- Cited by
- 499
- References
- 153
- Citations by year
- 2026: 46 · 2025: 70 · 2024: 92 · 2023: 60 · 2022: 51 · 2021: 63 · 2020: 57 · 2019: 29 · 2018: 14 · 2017: 7 · 2016: 8 · 2015: 1 · 2014: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NCI (P01-CA098993)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA double-strand breaks, chromatin, ionizing radiation, DNA damage mechanisms, DNA repair pathways, non-homologous end joining, homologous recombination, mutational burden, loss of heterozygosity, chromosomal rearrangements, nucleosome, chromatin structure, cell cycle, replication fork stalling, chromothripsis, chromosome coiling
- MeSH terms
- Animals, Cell Cycle, Chromatin, DNA Repair, Humans, Radiation, Ionizing, DNA Breaks, Double-Stranded, DNA End-Joining Repair
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