Activation of the Cellular DNA Damage Response in the Absence of DNA Lesions
Open accessAbstract
The cellular DNA damage response (DDR) is initiated by the rapid recruitment of repair factors to the site of DNA damage to form a multiprotein repair complex. How the repair complex senses damaged DNA and then activates the DDR is not well understood. We show that prolonged binding of DNA repair factors to chromatin can elicit the DDR in an ATM (ataxia telangiectasia mutated)– and DNAPK (DNA-dependent protein kinase)–dependent manner in the absence of DNA damage. Targeting of single repair factors to chromatin revealed a hierarchy of protein interactions within the repair complex and suggests amplification of the damage signal. We conclude that activation of the DDR does not require DNA damage and stable association of repair factors with chromatin is likely a critical step in triggering, amplifying, and maintaining the DDR signal.
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DNA damage response signaling can happen without a DNA lesion.
“This conclusion is in line with earlier tethering experiments demonstrating that a DNA lesion is not an obligatory part of the DDR machinery and DDR signaling can occur in its absence, allowing for the possibility of DDR initiation by stimuli other than DNA damage, such as chromatin structure (Bonilla et al., 2008; Soutoglou and Misteli, 2008).”
From Activation of DNA Damage Response Signaling by Condensed Chromatin (2014) · cites this paper as Soutoglou and Misteli, 2008
A DNA lesion is not required for the DNA damage response machinery.
“This conclusion is in line with earlier tethering experiments demonstrating that a DNA lesion is not an obligatory part of the DDR machinery and DDR signaling can occur in its absence, allowing for the possibility of DDR initiation by stimuli other than DNA damage, such as chromatin structure (Bonilla et al., 2008; Soutoglou and Misteli, 2008).”
From Activation of DNA Damage Response Signaling by Condensed Chromatin (2014) · cites this paper as Soutoglou and Misteli, 2008
The DDR activation by condensed chromatin is not due to DNA breaks induced by tethering, as no breaks were detected by TUNEL, Southern blot, or LM-PCR.
“No labeling by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was detected”
From Activation of DNA Damage Response Signaling by Condensed Chromatin (2014) · cites this paper as Soutoglou and Misteli, 2008
The MRN complex, MDC1, and H2AX are required for ATM recruitment to double-strand break sites for efficient ATM-mediated DDR activation.
“The MRN complex, MDC1, and H2AX are essential for the recruitment of ATM to the site of DSBs for efficient ATM-mediated DDR activation.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [219]
DDR activation requires stable association of DNA repair proteins in homologous recombination, not DNA damage itself.
“suggesting that DDR activation requires the stable association of DNA repair proteins in HR, but not DNA damage per se [219]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [219]
Prolonged chromatin binding by repair proteins such as Mre11, Nbs1, and MDC1 can trigger ATM-dependent DDR even without DNA damage.
“the prolonged binding to chromatin by repair proteins, such as Mre11, Nbs1 and MDC1, can elicit an ATM-dependent DDR in the absence of DNA damage”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [219]
Cites
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466 · see citing works
Chk1 and Chk2 kinases in checkpoint control and cancer
Bartek, J., & Lukas, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00110-7 · Cited by 1,513 · see citing works
Hickson, I., Zhao, Y., Richardson, C. J., Green, S. J., Martin, N. M. B., Orr, A. I., Reaper, P. M., Jackson, S. P., Curtin, N. J., & Smith, G. C. M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2727 · Cited by 1,220 · see citing works
Sensing and repairing DNA double-strand breaks
Jackson, S. P. (2002) · Carcinogenesis · doi:10.1093/carcin/23.5.687 · Cited by 1,126 · see citing works
Stucki, M., Clapperton, J. A., Mohammad, D. H., Yaffe, M. B., Smerdon, S. J., & Jackson, S. P. (2005) · Cell · doi:10.1016/j.cell.2005.09.038 · Cited by 1,103 · see citing works
Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks
Celeste, A., Fernandez-Capetillo, O., Kruhlak, M. J., Pilch, D. R., Staudt, D. W., Lee, A., Bonner, R. F., Bonner, W. M., & Nussenzweig, A. (2003) · Nature Cell Biology · doi:10.1038/ncb1004 · Cited by 989 · see citing works
MDC1 is a mediator of the mammalian DNA damage checkpoint
Stewart, G. S., Wang, B., Bignell, C. R., Taylor, A. M. R., & Elledge, S. J. (2003) · Nature · doi:10.1038/nature01446 · Cited by 874 · see citing works
DNA damage-induced G2–M checkpoint activation by histone H2AX and 53BP1
Fernández-Capetillo, Ó., Chen, H. T., Celeste, A., Ward, I. M., Romanienko, P. J., Morales, J. C., Naka, K., Xia, Z., Camerini‐Otero, R. D., Motoyama, N., et al. (2002) · Nature Cell Biology · doi:10.1038/ncb884 · Cited by 644 · see citing works
Lou, Z., Minter‐Dykhouse, K., Franco, S., Gostissa, M., Rivera, M. A., Celeste, A., Manis, J. P., van Deursen, J., Nussenzweig, A., Paull, T. T., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2005.11.025 · Cited by 629 · see citing works
Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
Bekker‐Jensen, S., Lukas, C., Kitagawa, R., Melander, F., Kastan, M. B., Bártek, J., & Lukas, J. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200510130 · Cited by 621 · see citing works
ATM and ATR: networking cellular responses to DNA damage
Shiloh, Y. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00159-3 · Cited by 601 · see citing works
Positional stability of single double-strand breaks in mammalian cells
Soutoglou, E., Dorn, J. F., Sengupta, K., Jasin, M., Nussenzweig, A., Ried, T., Danuser, G., & Misteli, T. (2007) · Nature Cell Biology · doi:10.1038/ncb1591 · Cited by 509 · see citing works
Self-citationMDC1 is required for the intra-S-phase DNA damage checkpoint
Goldberg, M., Stucki, M., Falck, J., D'Amours, D., Rahman, D., Pappin, D., Bartek, J., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature01445 · Cited by 506 · see citing works
Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage.
Lukas, C., Falck, J., Bartkova, J., Bartek, J., & Lukas, J. (2003) · Nature Cell Biology · doi:10.1038/ncb945 · Cited by 474 · see citing works
γH2AX and MDC1: Anchoring the DNA-damage-response machinery to broken chromosomes
Stucki, M., & Jackson, S. P. (2006) · DNA Repair · doi:10.1016/j.dnarep.2006.01.012 · Cited by 412 · see citing works
Mdc1 couples DNA double‐strand break recognition by Nbs1 with its H2AX‐dependent chromatin retention
Lukas, C., Melander, F., Stucki, M., Falck, J., Bekker‐Jensen, S., Goldberg, M., Lerenthal, Y., Jackson, S. P., Bártek, J., & Lukas, J. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600269 · Cited by 387 · see citing works
Bekker‐Jensen, S., Lukas, C., Melander, F., Bártek, J., & Lukas, J. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200503043 · Cited by 272 · see citing works
Peng, A., & Chen, P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300001200 · Cited by 97 · see citing works
DNA methylation promotes Aurora-B-driven phosphorylation of histone H3 in chromosomal subdomains
Monier, K., Mouradian, S., & Sullivan, K. F. (2006) · Journal of Cell Science · doi:10.1242/jcs.03326 · Cited by 60 · see citing works
Shiloh, Y. (2003) · Cell Cycle · doi:10.4161/cc.2.2.342 · Cited by 45 · see citing works
Watching the DNA Repair Ensemble Dance
Lukas, J., & Bártek, J. (2004) · Cell · doi:10.1016/j.cell.2004.09.006 · Cited by 27 · see citing works
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Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368 · see citing works
ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798 · see citing works
The ATM protein kinase: regulating the cellular response to genotoxic stress, and more
Shiloh, Y., & Ziv, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3546 · Cited by 1,649 · see citing works
-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin
Kinner, A., Wu, W., Staudt, C., & Iliakis, G. E. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn550 · Cited by 1,249 · see citing works
Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
Polo, S. E., & Jackson, S. P. (2011) · Genes & Development · doi:10.1101/gad.2021311 · Cited by 1,092 · see citing works
Doil, C., Mailand, N., Bekker‐Jensen, S., Ménard, P., Larsen, D. H., Pepperkok, R., Ellenberg, J., Panier, S., Durocher, D., Bártek, J., et al. (2009) · Cell · doi:10.1016/j.cell.2008.12.041 · Cited by 938 · see citing works
Role of oxidative stress and DNA damage in human carcinogenesis
Kryston, T. B., Georgiev, A. B., Pissis, P., & Georgakilas, A. G. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2010.12.016 · Cited by 927 · see citing works
Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
Lavin, M. F. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2514 · Cited by 901 · see citing works
Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation
Fumagalli, M., Rossiello, F., Clerici, M., Barozzi, S., Cittaro, D., Kaplunov, J. M., Bucci, G., Dobreva, M., Matti, V., Beausejour, C. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2466 · Cited by 851 · see citing works
ATM-Dependent Chromatin Changes Silence Transcription In cis to DNA Double-Strand Breaks
Shanbhag, N. M., Rafalska-Metcalf, I. U., Balane-Bolivar, C., Janicki, S. M., & Greenberg, R. A. (2010) · Cell · doi:10.1016/j.cell.2010.04.038 · Cited by 737 · see citing works
Sources of DNA Double-Strand Breaks and Models of Recombinational DNA RepairPreprint
Mehta, A., & Haber, J. E. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016428 · Cited by 727 · see citing works
Lysosome-mediated processing of chromatin in senescence
Ivanov, A., Pawlikowski, J., Manoharan, I., van Tuyn, J., Nelson, D. M., Rai, T. S., Shah, P. P., Hewitt, G., Korolchuk, V. I., Passos, J. F., et al. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201212110 · Cited by 539 · see citing works
Crosstalk between histone modifications during the DNA damage response
van Attikum, H., & Gasser, S. M. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.03.001 · Cited by 515 · see citing works
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Giglia‐Mari, G., Zotter, A., & Vermeulen, W. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000745 · Cited by 487 · see citing works
The emerging role of nuclear architecture in DNA repair and genome maintenance
Misteli, T., & Soutoglou, E. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2651 · Cited by 468 · see citing works
Self-citationPaull, T. T. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034335 · Cited by 458 · see citing works
Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons
Wang, W., Pan, L., Su, S. C., Quinn, E. J., Sasaki, M., Jimenez, J., Mackenzie, I. R., Huang, E. J., & Tsai, L. (2013) · Nature Neuroscience · doi:10.1038/nn.3514 · Cited by 433 · see citing works
Thompson, L. H. (2012) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2012.06.002 · Cited by 357 · see citing works
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Shiotani, B., & Zou, L. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.024 · Cited by 353 · see citing works
Assembly and function of DNA double-strand break repair foci in mammalian cells
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Ionizing-radiation induced DNA double-strand breaks: A direct and indirect lighting up
Vignard, J., Mirey, G., & Salles, B. (2013) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2013.06.013 · Cited by 319 · see citing works
Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all
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Schipler, A., & Iliakis, G. E. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt556 · Cited by 290 · see citing works
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Ács, K., Luijsterburg, M. S., Ackermann, L., Salomons, F. A., Hoppe, T., & Dantuma, N. P. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2188 · Cited by 280 · see citing works
Common mechanisms of PIKK regulation
Lovejoy, C. A., & Cortez, D. (2009) · DNA Repair · doi:10.1016/j.dnarep.2009.04.006 · Cited by 277 · see citing works
mTORC1 Signaling under Hypoxic Conditions Is Controlled by ATM-Dependent Phosphorylation of HIF-1α
Cam, H., Easton, J. B., High, A., & Houghton, P. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.030 · Cited by 266 · see citing works
Zhang, L., Wu, J., Ling, M. T., Zhao, L., & Zhao, K.-N. (2015) · Molecular Cancer · doi:10.1186/s12943-015-0361-x · Cited by 264 · see citing works
Double strand break repair functions of histone H2AX
Scully, R., & Xie, A. (2013) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2013.07.007 · Cited by 251 · see citing works
Yan, S., Sorrell, M., & Berman, Z. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1666-4 · Cited by 247 · see citing works
Extranuclear protection of chromosomal DNA from oxidative stress
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Nuclear position dictates DNA repair pathway choice
Lemaître, C., Grabarz, A., Tsouroula, K., Andronov, L., Furst, A., Pankotai, T., Heyer, V., Rogier, M., Attwood, K. M., Kessler, P., et al. (2014) · Genes & Development · doi:10.1101/gad.248369.114 · Cited by 209 · see citing works
Self-citationCostes, S. V., Chiolo, I., Pluth, J. M., Barcellos‐Hoff, M. H., & Jakob, B. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2009.12.006 · Cited by 204 · see citing works
Gillespie, K. A., Mehta, K. P. M., Laimins, L. A., & Moody, C. A. (2012) · Journal of Virology · doi:10.1128/jvi.00247-12 · Cited by 204 · see citing works
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Self-citationYuan, Y., Wang, Q., Paulk, J., Kubicek, S., Kemp, M. M., Adams, D., Shamji, A. F., Wagner, B. K., & Schreiber, S. L. (2012) · ACS Chemical Biology · doi:10.1021/cb300139y · Cited by 187 · see citing works
Nuclear Bodies: Random Aggregates of Sticky Proteins or Crucibles of Macromolecular Assembly?
Matera, A. G., Izaguire-Sierra, M., Praveen, K., & Rajendra, T. K. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.10.017 · Cited by 186 · see citing works
The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II
van der Weegen, Y., Golan-Berman, H., Mevissen, T. E. T., Apelt, K., González‐Prieto, R., Goedhart, J., Heilbrun, E. E., Vertegaal, A. C. O., van den Heuvel, D., Walter, J. C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15903-8 · Cited by 177 · see citing works
Recent developments in the use of γ -H2AX as a quantitative DNA double-strand break biomarker
Redon, C. E., Nakamura, A., Martin, O. A., Parekh, P. R., Weyemi, U., & Bonner, W. M. (2011) · Aging · doi:10.18632/aging.100284 · Cited by 172 · see citing works
H2AX Is Required for Cell Cycle Arrest via the p53/p21 Pathway
Fragkos, M., Jurvansuu, J., & Beard, P. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01830-08 · Cited by 170 · see citing works
Histone variants: emerging players in cancer biology
Vardabasso, C., Hasson, D., Ratnakumar, K., Chung, C., Duarte, L. F., & Bernstein, E. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1343-z · Cited by 167 · see citing works
DDB2 promotes chromatin decondensation at UV-induced DNA damage
Luijsterburg, M. S., Lindh, M., Ács, K., Vrouwe, M. G., Pines, A., van Attikum, H., Mullenders, L. H. F., & Dantuma, N. P. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201106074 · Cited by 155 · see citing works
Panier, S., Ichijima, Y., Fradet-Turcotte, A., Leung, C. C. Y., Kaustov, L., Arrowsmith, C. H., & Durocher, D. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.045 · Cited by 152 · see citing works
SIRT6 is a DNA double-strand break sensor
Onn, L., Portillo, M., Ilic, S., Cleitman, G., Stein, D., Kaluski, S., Shirat, I., Slobodnik, Z., Einav, M., Erdel, F., et al. (2020) · eLife · doi:10.7554/elife.51636 · Cited by 145 · see citing works
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Choi, J.-H., Lindsey‐Boltz, L. A., Kemp, M. G., Mason, A. C., Wold, M. S., & Sancar, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007856107 · Cited by 144 · see citing works
Tumors induce complex DNA damage in distant proliferative tissues in vivo
Redon, C. E., Dickey, J. S., Nakamura, A., Kareva, I., Näf, D., Nowsheen, S., Kryston, T. B., Bonner, W. M., Georgakilas, A. G., & Sedelnikova, O. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008260107 · Cited by 143 · see citing works
Reinson, T., Toots, M., Kadaja, M., Pipitch, R., Allik, M., Ustav, E., & Ustav, M. (2012) · Journal of Virology · doi:10.1128/jvi.01943-12 · Cited by 138 · see citing works
Fradet‐Turcotte, A., Bergeron-Labrecque, F., Moody, C. A., Lehoux, M., Laimins, L. A., & Archambault, J. (2011) · Journal of Virology · doi:10.1128/jvi.00542-11 · Cited by 135 · see citing works
Radiation-induced mitotic catastrophe in PARG-deficient cells
Amé, J., Fouquerel, E., Gauthier, L., Biard, D. S. F., Boussin, F. D., Dantzer, F., de MURCIA, G., & Schreiber, V. (2009) · Journal of Cell Science · doi:10.1242/jcs.039115 · Cited by 129 · see citing works
Eukaryotic DNA damage checkpoint activation in response to double-strand breaks
Finn, K., Lowndes, N. F., & Grenon, M. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0875-3 · Cited by 127 · see citing works
Pinato, S., Scandiuzzi, C., Arnaudo, N., Citterio, E., Gaudino, G., & Penengo, L. (2009) · BMC Molecular Biology · doi:10.1186/1471-2199-10-55 · Cited by 126 · see citing works
A direct role for small non-coding RNAs in DNA damage response
di Fagagna, F. D. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.09.008 · Cited by 125 · see citing works
Alternative Cyclin D1 Splice Forms Differentially Regulate the DNA Damage Response
Li, Z., Jiao, X., Wang, C., Shirley, L. A., Elsaleh, H., Dahl, O., Wang, M., Soutoglou, E., Knudsen, E. S., & Pestell, R. G. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0312 · Cited by 124 · see citing works
Self-citationZhao, J., Zhang, L., Lu, A., Han, Y., Colangelo, D., Bukata, C., Scibetta, A., Yousefzadeh, M. J., Li, X., Gurkar, A. U., et al. (2020) · Aging · doi:10.18632/aging.102863 · Cited by 122 · see citing works
Rajapakse, I., & Groudine, M. T. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201010129 · Cited by 122 · see citing works
A TFEB nuclear export signal integrates amino acid supply and glucose availability
Li, L., Friedrichsen, H. J., Andrews, S., Picaud, S., Volpon, L., Ngeow, K. C., Berridge, G., Fischer, R., Borden, K. L. B., Filippakopoulos, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04849-7 · Cited by 121 · see citing works
Choreography of recombination proteins during the DNA damage response
Lisby, M., & Rothstein, R. J. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.04.007 · Cited by 118 · see citing works
ATM protein kinase: the linchpin of cellular defenses to stress
Bhatti, S., Kozlov, S., Farooqi, A. A., Naqi, A., Lavin, M., & Khanna, K. K. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0683-9 · Cited by 116 · see citing works
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Lee, Y., Katyal, S., Li, Y., El‐Khamisy, S. F., Russell, H. R., Caldecott, K. W., & McKinnon, P. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2375 · Cited by 115 · see citing works
A new non‐catalytic role for ubiquitin ligase RNF8 in unfolding higher‐order chromatin structure
Luijsterburg, M. S., Ács, K., Ackermann, L., Wiegant, W. W., Bekker‐Jensen, S., Larsen, D. H., Khanna, K. K., van Attikum, H., Mailand, N., & Dantuma, N. P. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.104 · Cited by 113 · see citing works
Dealing with DNA damage: Relationships between checkpoint and repair pathways
Warmerdam, D. O., & Kanaar, R. (2009) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2009.12.001 · Cited by 113 · see citing works
The cellular response to DNA damage: A focus on MDC1 and its interacting proteins
Coster, G., & Goldberg, M. (2010) · Nucleus · doi:10.4161/nucl.1.2.11176 · Cited by 111 · see citing works
Nair, N., Shoaib, M., & Sørensen, C. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071486 · Cited by 98 · see citing works
Rupnik, A., Lowndes, N. F., & Grenon, M. (2009) · Chromosoma · doi:10.1007/s00412-009-0242-4 · Cited by 109 · see citing works
Assessment of functional effects of unclassified genetic variants
Couch, F. J., Rasmussen, L. J., Hofstra, R. M. W., Monteiro, Á. N. A., Greenblatt, M. S., de Wind, N., & for the IARC Unclassified Genetic Variants Working Group (2008) · Human Mutation · doi:10.1002/humu.20899 · Cited by 104 · see citing works
Viral and Cellular Genomes Activate Distinct DNA Damage Responses
Shah, G., & O’Shea, C. C. (2015) · Cell · doi:10.1016/j.cell.2015.07.058 · Cited by 103 · see citing works
Charting the Landscape of Tandem BRCT Domain–Mediated Protein Interactions
Woods, N. T., Mesquita, R. D., Sweet, M., Carvalho, M. A., Li, X., Liu, Y., Nguyen, H., Thomas, C. E., Iversen, E. S., Marsillac, S. M., et al. (2012) · Science Signaling · doi:10.1126/scisignal.2002255 · Cited by 103 · see citing works
Quin, J. E., Chan, K. T., Devlin, J. R., Cameron, D. P., Diesch, J., Cullinane, C. M., Ahern, J., Khot, A. S., Hein, N., George, A. J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10452 · Cited by 103 · see citing works
Iliakis, G. E., Mladenov, E., & Mladenova, V. (2019) · Cancers · doi:10.3390/cancers11111671 · Cited by 101 · see citing works
Destabilization of linker histone H1.2 is essential for ATM activation and DNA damage repair
Li, Z., Li, Y., Tang, M., Peng, B., Lu, X., Yang, Q., Zhu, Q., Hou, T., Li, M., Liu, C., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0048-0 · Cited by 99 · see citing works
The Carboxyl Terminus of Brca2 Links the Disassembly of Rad51 Complexes to Mitotic Entry
Ayoub, N., Rajendra, E., Su, X., Jeyasekharan, A. D. D., Mahen, R., & Venkitaraman, A. R. (2009) · Current Biology · doi:10.1016/j.cub.2009.05.057 · Cited by 99 · see citing works
Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks
Gobbini, E., Cesena, D., Galbiati, A., Lockhart, A., & Longhese, M. P. (2013) · DNA Repair · doi:10.1016/j.dnarep.2013.07.009 · Cited by 98 · see citing works
A limited number of double-strand DNA breaks is sufficient to delay cell cycle progression
van den Berg, J., Manjón, A. G., Kielbassa-Elkadi, K., Feringa, F. M., Freire, R., & Medema, R. H. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky786 · Cited by 96 · see citing works
Rochman, M., Postnikov, Y. V., Correll, S., Malicet, C., Wincovitch, S., Karpova, T., McNally, J. G., Wu, X., Bubunenko, N. A., Grigoryev, S. A., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.07.002 · Cited by 96 · see citing works
Checkpoint mechanisms at the intersection between DNA damage and repair
Lazzaro, F., Giannattasio, M., Puddu, F., Granata, M., Pellicioli, A., Plevani, P., & Muzi-Falconi, M. (2009) · DNA Repair · doi:10.1016/j.dnarep.2009.04.022 · Cited by 94 · see citing works
The emergence of lineage-specific chromosomal topologies from coordinate gene regulation
Rajapakse, I., Perlman, M. D., Scalzo, D., Kooperberg, C. L., Groudine, M. T., & Kosak, S. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900986106 · Cited by 94 · see citing works
The Nuclear Oncogene SET Controls DNA Repair by KAP1 and HP1 Retention to Chromatin
Kalousi, A., Hoffbeck, A.-S., Selemenakis, P., Pinder, J. B., Savage, K. I., Khanna, K. K., Brino, L., Dellaire, G., Gorgoulis, V. G., & Soutoglou, E. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.005 · Cited by 92 · see citing works
Self-citationMultiple DNA Damage Signaling and Repair Pathways Deregulated by Simian Virus 40 Large T Antigen
Boichuk, S., Hu, L., Hein, J., & Gjoerup, O. V. (2010) · Journal of Virology · doi:10.1128/jvi.00334-10 · Cited by 89 · see citing works
Luijsterburg, M. S., Typas, D., Caron, M., Wiegant, W. W., van den Heuvel, D., Boonen, R. A. C. M., Couturier, A. M., Mullenders, L. H. F., Masson, J., & van Attikum, H. (2017) · eLife · doi:10.7554/elife.20922 · Cited by 88 · see citing works
Bouquet, F., Ousset, M., Biard, D. S. F., Fallone, F., Dauvillier, S., Frit, P., Salles, B., & Muller, C. (2011) · Journal of Cell Science · doi:10.1242/jcs.078030 · Cited by 88 · see citing works
Molecular damage in cancer: an argument for mTOR-driven aging
Blagosklonny, M. V. (2011) · Aging · doi:10.18632/aging.100422 · Cited by 87 · see citing works
Recognition of DNA damage by XPC coincides with disruption of the XPC–RAD23 complex
Bergink, S., Toussaint, W., Luijsterburg, M. S., Dinant, C., Alekseev, S., Hoeijmakers, J. H. J., Dantuma, N. P., Houtsmuller, A. B., & Vermeulen, W. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201107050 · Cited by 86 · see citing works
Woods, N. T., Baskin, R., Golubeva, V. A., Jhuraney, A., Gregoriis, G. D., Vaclová, T., Goldgar, D. E., Couch, F. J., Carvalho, M. A., Iversen, E. S., et al. (2016) · npj Genomic Medicine · doi:10.1038/npjgenmed.2016.1 · Cited by 84 · see citing works
Perspectives on the DNA damage and replication checkpoint responses in Saccharomyces cerevisiae
Putnam, C. D., Jaehnig, E. J., & Kolodner, R. D. (2009) · DNA Repair · doi:10.1016/j.dnarep.2009.04.021 · Cited by 83 · see citing works
Bohgaki, T., Bohgaki, M., Cardoso, R., Panier, S., Zeegers, D., Li, L., Stewart, G. S., Sanchez, O. H., Hande, M. P., Durocher, D., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001381 · Cited by 83 · see citing works
Non‐coding RNAs in DNA damage and repair
Sharma, V., & Misteli, T. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.05.006 · Cited by 83 · see citing works
Self-citationDNA double-strand break signaling and human disorders
Bohgaki, T., Bohgaki, M., & Hakem, R. (2010) · Genome Integrity · doi:10.1186/2041-9414-1-15 · Cited by 83 · see citing works
Chung, I., Leonhardt, H., & Rippe, K. (2011) · Journal of Cell Science · doi:10.1242/jcs.084681 · Cited by 83 · see citing works
A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene
Singh, H. R., Nardozza, A. P., Möller, I. R., Knobloch, G., Kistemaker, H. A. V., Hassler, M., Harrer, N., Blessing, C., Eustermann, S., Kotthoff, C., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.11.019 · Cited by 82 · see citing works
Is DNA damage indispensable for stress-induced senescence?
Bielak-Żmijewska, A., Mosieniak, G., & Sikora, E. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.004 · Cited by 80 · see citing works
Effects of hyperthermia as a mitigation strategy in DNA damage-based cancer therapies
Mantso, T., Goussetis, G., Franco, R., Botaitis, S., Pappa, A., & Panayiotidis, M. I. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2016.03.004 · Cited by 80 · see citing works
CIRKIL Exacerbates Cardiac Ischemia/Reperfusion Injury by Interacting With Ku70
Xiao, H., Zhang, M., Wu, H., Wu, J., Hu, X., Pei, X., Li, D., Zhao, L., Hua, Q., Meng, B., et al. (2022) · Circulation Research · doi:10.1161/circresaha.121.318992 · Cited by 79 · see citing works
γ-H2AX as a biomarker for DNA double-strand breaks in ecotoxicology
Gerić, M., Gajski, G., & Garaj‐Vrhovac, V. (2014) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2014.03.035 · Cited by 79 · see citing works
Menegakis, A., Yaromina, A., Eicheler, W., Dörfler, A., Beuthien‐Baumann, B., Thames, H. D., Baumann, M. A., & Krause, M. (2009) · International Journal of Radiation Biology · doi:10.3109/09553000903242149 · Cited by 76 · see citing works
Li, W., Zhao, L., Zang, W., Liu, Z., Chen, L., Liu, T., Xu, D., & Jia, J. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.11.045 · Cited by 75 · see citing works
The DNA Damage Response Induced by Infection with Human Cytomegalovirus and Other Viruses
Xiaofei, E., & Kowalik, T. F. (2014) · Viruses · doi:10.3390/v6052155 · Cited by 75 · see citing works
The RBBP6/ZBTB38/MCM10 Axis Regulates DNA Replication and Common Fragile Site Stability
Miotto, B., Chibi, M., Xie, P., Koundrioukoff, S., Moolman-Smook, H., Pugh, D. J. R., Debatisse, M., He, F.-C., Zhang, L., & Defossez, P. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.030 · Cited by 74 · see citing works
Krynetskaia, N. F., Phadke, M. S., Jadhav, S. H., & Krynetskiy, E. Y. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0695 · Cited by 73 · see citing works
Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response
Sitz, J., Blanchet, S. A., Gameiro, S. F., Biquand, É., Morgan, T., Galloy, M., Dessapt, J., Lavoie, É. G., Blondeau, A., Smith, B. C., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906102116 · Cited by 72 · see citing works
- Authors
- Soutoglou, E., & Misteli, T.
- Affiliations
- National Institutes of Health (US)
- Venue
- Science
- Published
- 2008-06-13
- Volume
- 320
- Issue
- 5882
- Pages
- 1507-1510
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2575099
- OpenAlex
- W2067328670
- Cited by
- 299
- References
- 21
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 11 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 15 · 2014: 26 · 2013: 21 · 2012: 19
- FWCI
- 15.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (Z01BC010309)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- DNA damage response, ATM, DNA repair proteins, chromatin binding, signal amplification, protein-protein interaction
- MeSH terms
- Tumor Suppressor p53-Binding Protein 1, Checkpoint Kinase 1, MRE11 Homologue Protein, Animals, Cell Cycle, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, DNA Damage, DNA Repair, DNA-Binding Proteins, Histones, Nuclear Proteins, Phosphorylation, Protein Kinases, Recombinant Fusion Proteins, Signal Transduction, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, NIH 3T3 Cells, DNA Repair Enzymes, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2
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