The methyl methanesulfonate induced S-phase delay in XRCC1-deficient cells requires ATM and ATR
Abstract
X-ray repair cross-complementing 1 (XRCC1) is required for DNA single-strand break and base excision repair (BER) in human cells. XRCC1-deficient human cells show hypersensitivity to cell killing, increased genetic instability and a significant delay in S-phase progression after exposure to the alkylating agent methyl methanesulfonate (MMS). Using RNAi modulation of XRCC1 levels, we show here that this S-phase delay is associated with significantly increased levels of recombinational repair as visualized by Rad51 focus formation. Using ATM- and ATR-defective cells and an ATM specific kinase inhibitor we demonstrate for the first time that the MMS-induced S-phase checkpoint requires both ATM and ATR. This unique dependency is associated with phosphorylation of ATM/ATR downstream targets or effectors such as SMC1 and Chk1. These results support the hypothesis that after MMS-treatment, the presence of unresolved BER intermediates gives rise to lesions that activate both ATM and ATR and that during the consequent S-phase delay, such intermediates may be repaired by a recombinational pathway which involves the Rad51 protein.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In XRCC1-deficient cells, MMS produces unresolved BER intermediates and turns on ATM- and ATR-dependent DDR pathways, including S-phase delay and phosphorylation of SMC1 at serine 966 and Chk1 at serine 345.
“MMS induces unresolved BER intermediates in XRCC1-deficient cells and activates ATM and ATR-dependent DDR pathways, including S-phase delay and SMC1 (structural maintenance of chromosomes protein 1) phosphorylation at Serine 966 and Chk1 phosphorylation at Serine 345 [199]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [199]
Cites
Instability and decay of the primary structure of DNA
Lindahl, T. (1993) · Nature · doi:10.1038/362709a0 · Cited by 5,679 · see citing works
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Zou, L., & Elledge, S. J. (2003) · Science · doi:10.1126/science.1083430 · Cited by 2,693 · see citing works
Cell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966 · see citing works
Lindahl, T. L., & Wood, R. D. (1999) · Science · doi:10.1126/science.286.5446.1897 · Cited by 1,489 · see citing works
ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex
Lee, J.-H., & Paull, T. T. (2005) · Science · doi:10.1126/science.1108297 · Cited by 1,424 · 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
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G. C. M., Lukas, J., & Jackson, S. P. (2006) · Nature Cell Biology · doi:10.1038/ncb1337 · Cited by 1,064 · see citing works
ATR and ATRIP: Partners in Checkpoint Signaling
Cortez, D., Guntuku, S., Qin, J., & Elledge, S. J. (2001) · Science · doi:10.1126/science.1065521 · Cited by 985 · see citing works
Checking on DNA damage in S phase
Bartek, J., Lukas, C., & Lukas, J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1493 · Cited by 758 · see citing works
XRCC1 and DNA strand break repair
Caldecott, K. W. (2003) · DNA repair · doi:10.1016/s1568-7864(03)00118-6 · Cited by 598 · see citing works
Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damagePreprint
Kim, S., Xu, B., & Kastan, M. B. (2002) · Genes & Development · doi:10.1101/gad.970602 · Cited by 581 · see citing works
PARP is important for genomic stability but dispensable in apoptosisPreprint
Wang, Z., Stingl, L., Morrison, C. G., Jantsch, M. F., Łoś, M., Schulze‐Osthoff, K., & Wagner, E. F. (1997) · Genes & Development · doi:10.1101/gad.11.18.2347 · Cited by 557 · see citing works
Cliby, W. A., Roberts, C. J., Cimprich, K. A., Stringer, C. M., Lamb, J. R., Schreiber, S. L., & Friend, S. H. (1998) · The EMBO Journal · doi:10.1093/emboj/17.1.159 · Cited by 534 · see citing works
SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpointPreprint
Yazdi, P. T., Wang, Y., Zhao, S., Patel, N., Lee, E. Y.-H. P., & Qin, J. (2002) · Genes & Development · doi:10.1101/gad.970702 · Cited by 505 · see citing works
Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatinPreprint
Zou, L., Cortez, D., & Elledge, S. J. (2002) · Genes & Development · doi:10.1101/gad.950302 · Cited by 498 · see citing works
Two Molecularly Distinct G2/M Checkpoints Are Induced by Ionizing Irradiation
Xu, B., Kim, S., Lim, D., & Kastan, M. B. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1049-1059.2002 · Cited by 470 · see citing works
Thompson, L. H., Brookman, K. W., Jones, N. J., Allen, S. A., & Carrano, A. V. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.12.6160 · Cited by 404 · see citing works
A Central Role for DNA Replication Forks in Checkpoint Activation and Response
Tercero, J. A., Longhese, M. P., & Diffley, J. F. X. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00169-2 · Cited by 394 · see citing works
Stiff, T., Walker, S. A., Cerosaletti, K., Goodarzi, A. A., Petermann, E., Concannon, P., O'Driscoll, M., & Jeggo, P. A. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601446 · Cited by 360 · see citing works
Requirement for theXrcc1DNA Base Excision Repair Gene during Early Mouse Development
Tebbs, R. S., Flannery, M. L., Meneses, J. J., Hartmann, A., Tucker, J. D., Thompson, L. H., Cleaver, J. E., & Pedersen, R. A. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9232 · Cited by 337 · see citing works
Involvement of poly(ADP-ribose) polymerase in base excision repair
Dantzer, F., Schreiber, V., Niedergang, C., Trucco, C., Flatter, E., de la Rubia, G., Oliver, J., Rolli, V., Murcia, J. M., & de MURCIA, G. (1999) · Biochimie · doi:10.1016/s0300-9084(99)80040-6 · Cited by 327 · see citing works
Thompson, L. H., Brookman, K. W., Dillehay, L. E., Carrano, A. V., Mazrimas, J. A., Mooney, C. L., & Minkler, J. L. (1982) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(82)90276-7 · Cited by 321 · see citing works
Pathways for mitotic homologous recombination in mammalian cells
Helleday, T. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.013 · Cited by 314 · see citing works
Rapid Activation of ATR by Ionizing Radiation Requires ATM and Mre11
Myers, J. S., & Cortez, D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513265200 · Cited by 294 · see citing works
Rescue of arrested replication forks by homologous recombination
Michel, B., Flores, M. J., Viguera, E., Grompone, G., Seigneur, M., & Bidnenko, V. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111008798 · Cited by 292 · see citing works
ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses
Bao, S., Tibbetts, R. S., Brumbaugh, K. M., Fang, Y., Richardson, D. A., Ali, A., Chen, S. M., Abraham, R. T., & Wang, X.-F. (2001) · Nature · doi:10.1038/35082110 · Cited by 279 · see citing works
ATM regulates ATR chromatin loading in response to DNA double-strand breaks
Cuadrado, M., Martinez-Pastor, B., Murga, M., Toledo, L. I., Gutierrez-Martinez, P., Lopez, E., & Fernandez-Capetillo, O. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051923 · Cited by 232 · see citing works
Methylation-induced blocks to in vitro DNA replication
Larson, K. L., Sahm, J., Shenkar, R., & Bs, S. (1985) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(85)90103-4 · Cited by 223 · see citing works
Kuzminov, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151260698 · Cited by 217 · see citing works
Bryant, H. E. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl108 · Cited by 208 · see citing works
Genetic Analysis of Yeast RPA1 Reveals Its Multiple Functions in DNA Metabolism
Umezu, K., Sugawara, N., Chen, C., Haber, J. E., & Kolodner, R. D. (1998) · Genetics · doi:10.1093/genetics/148.3.989 · Cited by 206 · see citing works
BRCA2-dependent and independent formation of RAD51 nuclear foci
Tarsounas, M., Davies, D. C., & West, S. C. (2003) · Oncogene · doi:10.1038/sj.onc.1206263 · Cited by 205 · see citing works
XRCC1 is required for DNA single-strand break repair in human cells
Brem, R. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki543 · Cited by 201 · see citing works
Self-citationRegulation of DNA replication by ATR: signaling in response to DNA intermediates
Shechter, D., Costanzo, V., & Gautier, J. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.03.020 · Cited by 198 · see citing works
ATM and ATR: Components of an Integrated Circuit
Hurley, P. J., & Bunz, F. (2007) · Cell Cycle · doi:10.4161/cc.6.4.3886 · Cited by 196 · see citing works
Base Excision Repair Intermediates Induce p53-independent Cytotoxic and Genotoxic Responses
Sobol, R. W., Kartalou, M., Almeida, K. H., Joyce-Gray, D. F., Engelward, B. P., Horton, J. K., Prasad, R., Samson, L. D., & Wilson, S. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306592200 · Cited by 183 · see citing works
Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway
Alderton, G. K., Joenje, H., Varon, R., Børglum, A. D., Jeggo, P. A., & O’Driscoll, M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh335 · Cited by 177 · see citing works
Hernes, T. A. N., Haug, T., Singh, K. K., Keshav, K. F., Skorpen, F., Otterlei, M., Bharati, S., Lindmo, T., Bénichou, S., Bénarous, R., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.10.6561 · Cited by 150 · see citing works
Protein–protein interactions and posttranslational modifications in mammalian base excision repair
Fan, J., & WILSONIII, D. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.01.012 · Cited by 144 · see citing works
Fernet, M., Gribaa, M., Salih, M. A. M., Seidahmed, M. Z., Hall, J. A., & Koenig, M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi027 · Cited by 143 · see citing works
Self-citationProliferation is a prerequisite for bacterial superantigen-induced T cell apoptosis in vivo.
Renno, T., Hahne, M., & MacDonald, H. R. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.6.2283 · Cited by 123 · see citing works
Jongmans, W., Vuillaume, M., Chrzańowska, K., Smeets, D., Sperling, K., & Hall, J. A. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5016 · Cited by 117 · see citing works
Self-citationKaina, B. (2004) · Cytogenetic and Genome Research · doi:10.1159/000077469 · Cited by 115 · see citing works
You, Z., Kong, L., & Newport, J. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204120200 · Cited by 114 · see citing works
SMC1 involvement in fragile site expression
Musio, A., Montagna, C., Mariani, T., Tilenni, M., Focarelli, M. L., Brait, L., Indino, E., Benedetti, P. A., Chessa, L., Albertini, A., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi049 · Cited by 104 · see citing works
Parlanti, E., Locatelli, G. A., Maga, G., & Eugenia Dogliotti, Y. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl1159 · Cited by 101 · see citing works
Hus1 Acts Upstream of Chk1 in a Mammalian DNA Damage Response Pathway
Weiss, R. S., Matsuoka, S., Elledge, S. J., & Leder, P. (2002) · Current Biology · doi:10.1016/s0960-9822(01)00626-1 · Cited by 91 · see citing works
ATM is required for the cellular response to thymidine induced replication fork stress
Bolderson, E., Scorah, J., Helleday, T., Smythe, C., & Meuth, M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh316 · Cited by 86 · see citing works
DNA replication is required for the checkpoint response to damaged DNA in Xenopus egg extracts
Stokes, M. P., Hatten, R. A. V., Lindsay, H. D., & Michael, W. M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200204127 · Cited by 82 · see citing works
Pascucci, B. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki168 · Cited by 77 · see citing works
Horton, J. K., Stefanick, D. F., Naron, J. M., Kedar, P. S., & Wilson, S. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413841200 · Cited by 63 · see citing works
Carrano, A. V., Minkler, J. L., Dillehay, L. E., & Thompson, L. H. (1986) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(86)90090-4 · Cited by 46 · see citing works
Ray, J. H., Altenburg, L. C., & Jacobs, M. M. (1978) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(78)90220-8 · Cited by 30 · see citing works
Hypersensitivity of ataxia telangiectasia skin fibroblasts to DNA alkylating agents
Barfknecht, T. R., & Little, J. B. (1982) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(82)90299-8 · Cited by 29 · see citing works
Mechanism Underlying Replication Protein A Stimulation of DNA Ligase I
Ranalli, T. A., DeMott, M. S., & Bambara, R. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109053200 · Cited by 26 · see citing works
Horton, J. K., Stefanick, D. F., Kedar, P. S., & Wilson, S. H. (2007) · DNA repair · doi:10.1016/j.dnarep.2006.12.015 · Cited by 25 · see citing works
The novel gene mus7+ is involved in the repair of replication-associated DNA damage in fission yeast
Yokoyama, M., Inoue, H., Ishii, C., & Murakami, Y. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.01.005 · Cited by 18 · see citing works
Identification of sequences that target BRCA1 to nuclear foci following alkylative DNA damage
Au, W. W. Y., & Henderson, B. R. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.04.010 · Cited by 16 · see citing works
Ray, J. H., Altenburg, L. C., & Jacobs, M. M. (1978) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(78)90286-5 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
DNA breaks and chromosomal aberrations arise when replication meets base excision repair
Ensminger, M., Iloff, L., Ebel, C., Nikolova, T., Kaina, B., & Löbrich, M. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201312078 · Cited by 138 · see citing works
Chk2-dependent phosphorylation of XRCC1 in the DNA damage response promotes base excision repair
Chou, W., Wang, H., Wong, F., Ding, S., Wu, P., Shieh, S., & Shen, C. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.229 · Cited by 104 · see citing works
Groth, P., Ausländer, S., Majumder, M. M., Schultz, N., Johansson, F., Petermann, E., & Helleday, T. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.07.010 · Cited by 80 · see citing works
Nikolova, T., Ensminger, M., Löbrich, M., & Kaina, B. (2010) · DNA repair · doi:10.1016/j.dnarep.2010.07.005 · Cited by 75 · see citing works
Składanowski, A., Bozko, P. M., & Sabisz, M. (2009) · Chemical Reviews · doi:10.1021/cr900026u · Cited by 71 · see citing works
Abdel-Fatah, T. M. A., Arora, A., Moseley, P. M., Coveney, C., Perry, C., Johnson, K., Kent, C. D., Ball, G., Chan, S. Y. T., & Madhusudan, S. (2014) · BBA Clinical · doi:10.1016/j.bbacli.2014.08.001 · Cited by 60 · see citing works
Initiation of the ATM-Chk2 DNA damage response through the base excision repair pathway
Chou, W., Hu, L., Hsiung, C., & Shen, C. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv079 · Cited by 47 · see citing works
Chalony, C. L., Hoffschir, F., Gauthier, L., Gross, J., Biard, D. S. F., Boussin, F. D., & Pennaneach, V. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0975-8 · Cited by 32 · see citing works
Lévy, N., Oehlmann, M., Delalande, F., Nasheuer, H., DORSSELAER, A. V., Schreiber, V., de MURCIA, G., Murcia, J. M., Maiorano, D., & Bresson, A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp144 · Cited by 28 · see citing works
Palomino, G. M., Bassi, C. L., Wastowski, I. J., Xavier, D. J., Lucisano-Valim, Y. M., Crispim, J. C. O., Rassi, D. M., Marques-Neto, J. F., Sakamoto‐Hojo, E. T., Moreau, P., et al. (2014) · The Journal of Rheumatology · doi:10.3899/jrheum.130376 · Cited by 25 · see citing works
Carrozza, M. J., Stefanick, D. F., Horton, J. K., Kedar, P. S., & Wilson, S. H. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.07.010 · Cited by 23 · see citing works
Distinct regulation of ATM signaling by DNA single-strand breaks and APE1
Zhao, H., Li, J., You, Z., Lindsay, H. D., & Yan, S. (2024) · Nature Communications · doi:10.1038/s41467-024-50836-6 · Cited by 21 · see citing works
Yin, Z., Chen, E., Cai, X., Gong, E., Li, Y., Xu, C., Ye, Z., Cao, Z., & Pan, J. (2021) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2021.1892132 · Cited by 17 · see citing works
Badjatia, N., Nguyen, T. N., Lee, J. H., & Günzl, A. (2013) · Molecular Microbiology · doi:10.1111/mmi.12435 · Cited by 14 · see citing works
Repair of endogenous DNA base lesions modulate lifespan in mice
Meira, L. B., Calvo, J. A., Shah, D., Klapacz, J., Moroski-Erkul, C. A., Bronson, R. T., & Samson, L. D. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.05.012 · Cited by 12 · see citing works
Distinct roles of XRCC1 in genome integrity in Xenopus egg extracts
Cupello, S., Lin, Y., & Yan, S. (2019) · Biochemical Journal · doi:10.1042/bcj20190798 · Cited by 11 · see citing works
Pan, Y., Yuan, D., Zhang, J., Xu, P., Chen, H., & Shao, C. (2009) · Radiation Research · doi:10.1667/rr1491.1 · Cited by 9 · see citing works
Tracing the evolution: a review of dictionary-learning in ATR systems
Obaideen, K., Faroukh, Y., & Al-Shabi, M. A. (2024) · Automatic target recognition. Conference · doi:10.1117/12.3013812
- Authors
- Brem, R., Fernet, M., Chapot, B., & Hall, J.
- Affiliations
- Centre international de recherche sur le cancer (FR)
- Inserm (FR)
- Corresponding author
- Hall, Janet
- Venue
- DNA Repair
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 7
- Issue
- 6
- Pages
- 849-857
- ISSN
- 1568-7856 (ISSN-L)
- 1568-7864
- OpenAlex
- W2094663394
- Cited by
- 20
- References
- 59
- Citations by year
- 2024: 2 · 2021: 1 · 2019: 1 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- DNA repair (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre International de Recherche sur le Cancer
- Electricité de France
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- XRCC1, methyl methanesulfonate, S-phase checkpoint, ATM, ATR, base excision repair, single-strand breaks, recombinational repair, RAD51 foci, Chk1 phosphorylation, DNA damage response, alkylating agents, genomic instability
- MeSH terms
- X-ray Repair Cross Complementing Protein 1, DNA-Binding Proteins, Flow Cytometry, Fluorescent Antibody Technique, Humans, Methyl Methanesulfonate, Phosphorylation, Signal Transduction, S Phase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, RNA Interference, Cell Line, Tumor, Ataxia Telangiectasia Mutated Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
