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γH2AX foci on apparently intact mitotic chromosomes: Not signatures of misrejoining events but signals of unresolved DNA damage

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Pages 3026-3036 | Received 19 Mar 2014, Accepted 07 Jul 2014, Published online: 30 Oct 2014

References

  • Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ. ATM Phosphorylates Histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001; 276:42462-7; PMID:11571274; http://dx.doi.org/10.1074/jbc.C100466200
  • Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson S. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 2005; 123:1213-26; PMID:16377563; http://dx.doi.org/10.1016/j.cell.2005.09.038
  • Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on Serine 139. J Biol Chem 1998; 273:5858-68; PMID:9488723; http://dx.doi.org/10.1074/jbc.273.10.5858
  • Cleaver JE. γH2Ax: Biomarker of damage or functional participant in DNA repair “All that Glitters is not Gold!” Photochem Photobiol 2011; 87:1230-9; PMID:21883247; http://dx.doi.org/10.1111/j.1751-1097.2011.00995.x
  • Chen HT, Bhandoola A, Difilippantonio MJ, Zhu J, Brown MJ, Tai X, Rogakou EP, Brotz TM, Bonner WM, Ried Tet al. Response to RAG-mediated V(D)J cleavage by NBS1 and g-H2AX. Science 2000; 290:1962-4; PMID:11110662; http://dx.doi.org/10.1126/science.290.5498.1962
  • Rogakou EP, Boon C, Redon C, Bonner WM. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 1999; 146:905-16; PMID:10477747; http://dx.doi.org/10.1083/jcb.146.5.905
  • Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at Serine 139. J Biol Chem 2000; 275:9390-5; PMID:10734083; http://dx.doi.org/10.1074/jbc.275.13.9390
  • Celeste A, Fernandez-Capetillo O, Kruhlak MJ, Pilch DR, Staudt DW, Lee A, Bonner RF, Bonner WM, Nussenzweig A. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol 2003; 5:675-9; PMID:12792649; http://dx.doi.org/10.1038/ncb1004
  • Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 2000; 10:886-95; PMID:10959836; http://dx.doi.org/10.1016/S0960-9822(00)00610-2
  • Bassing CH, Chua KF, Sekiguchi J, Suh H, Whitlow SR, Fleming JC, Monroe BC, Ciccone DN, Yan C, Vlasakova K, et al. Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX. Proc Nat Acad Sci U S A 2002; 99:8173-8; PMID:12034884; http://dx.doi.org/10.1073/pnas.122228699
  • Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ, et al. Genomic instability in mice lacking histone H2AX. Science 2002; 296:922-7; PMID:11934988; http://dx.doi.org/10.1126/science.1069398
  • Löbrich M, Shibata A, Beucher A, Fisher A, Ensminger M, Goodarzi AA, Barton O, Jeggo PA. γH2AX foci analysis for monitoring DNA double-strand break repair: Strengths, limitations and optimization. Cell Cycle 2010; 9:662-9; PMID:20139725; http://dx.doi.org/10.4161/cc.9.4.10764
  • Bonner WM, Redon CE, Dickey JS, Nakamura AJ, Sedelnikova OA, Solier S, Pommier Y. gammaH2AX and cancer. Nat Rev Cancer 2008; 8:957-67; PMID:19005492; http://dx.doi.org/10.1038/nrc2523
  • Kinner A, Wu W, Staudt C, Iliakis G. Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucl Acids Res 2008; 36:5678-94; PMID:18772227; http://dx.doi.org/10.1093/nar/gkn550
  • Rothkamm K, Lobrich M. Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Nat Acad Sci 2003; 100:5057-62; PMID:12679524; http://dx.doi.org/10.1073/pnas.0830918100
  • Sedelnikova OA, Rogakou EP, Panyutin IG, Bonner WM. Quantitative detection of 125IdU-induced DNA double-strand breaks with gamma-H2AX antibody. Radiat Res 2002:486-92; PMID:12236816; http://dx.doi.org/10.1667/0033-7587(2002)158[0486:QDOIID]2.0.CO;2
  • Foster ER, Downs JA. Histone H2A phosphorylation in DNA double-strand break repair. FEBS J 2005; 272:3231-40; PMID:15978030; http://dx.doi.org/10.1111/j.1742-4658.2005.04741.x
  • Forand A, Dutrillaux B, Bernardino-Sgherri J. Gamma-H2AX expression pattern in non-irradiated neonatal mouse germ cells and after low-dose gamma-radiation: relationships between chromatid breaks and DNA double-strand breaks. Biol Reprod 2004; 71:643-9; PMID:15115728; http://dx.doi.org/10.1095/biolreprod.104.027466
  • Kato TA, Nagasawa H, Weil MM, Little JB, Bedford JS. Levels of gamma-H2AX Foci after low-dose-rate irradiation reveal a DNA DSB rejoining defect in cells from human ATM heterozygotes in two at families and in another apparently normal individual. Radiat Res 2006; 166:443-53; PMID:18179804; PMID:16953663; http://dx.doi.org/10.1667/RR3604.1
  • Kato TA, Okayasu R, Bedford JS. Comparison of the induction and disappearance of DNA double strand breaks and γ-H2AX foci after irradiation of chromosomes in G1-phase or in condensed metaphase cells. Mutat Res/Fund Mol Mech Mutagen 2008; 639:108-12; http://dx.doi.org/10.1016/j.mrfmmm.2007.11.006
  • McManus KJ, Hendzel MJ. ATM-dependent DNA damage-independent mitotic phosphorylation of H2AX in normally growing mammalian cells. Mol Biol Cell 2005; 16:5013-25; PMID:16030261; http://dx.doi.org/10.1091/mbc.E05-01-0065
  • Suzuki M, Suzuki K, Kodama S, Watanabe M. Phosphorylated histone H2AX foci persist on rejoined mitotic chromosomes in normal human diploid cells exposed to ionizing radiation. Radiat Res 2006; 165:269-76; PMID:16494514; http://dx.doi.org/10.1667/RR3508.1
  • Ichijima Y, Sakasai R, Okita N, Asahina K, Mizutani S, Teraoka H. Phosphorylation of histone H2AX at M phase in human cells without DNA damage response. Biochem Biophys Res Commun 2005; 336:807-12; PMID:16153602; http://dx.doi.org/10.1016/j.bbrc.2005.08.164
  • Kato TA, Okayasu R, Bedford JS. Signatures of DNA double strand breaks produced in irradiated G1 and G2 cells persist into mitosis. J Cell Physiol 2009; 219:760-5; PMID:19206160; http://dx.doi.org/10.1002/jcp.21726
  • Svetlova MP, Solovjeva LV, Tomilin NV. Mechanism of elimination of phosphorylated histone H2AX from chromatin after repair of DNA double-strand breaks. Mutat Res/Fund Mol Mech Mutagen 2010; 685:54-60; PMID:19682466; http://dx.doi.org/10.1016/j.mrfmmm.2009.08.001
  • Ward IM, Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 2001; 276:47759-62; PMID:11673449; http://dx.doi.org/10.1074/jbc.M009785200
  • Martín M, Genescà  A, Latre L, Ribas M, Miró R, Egozcue J, Tusell L. Radiation-induced chromosome breaks in ataxia-telangiectasia cells remain open. Int J Radiat Biol 2003; 79:203-10; PMID:12745885; http://dx.doi.org/10.1080/0955300031000089601
  • Martín M, Terradas M, Iliakis G, Tusell L, Genescà A. Breaks invisible to the DNA damage response machinery accumulate in ATM-deficient cells. Genes, Chromosome Cancer 2009; 48:745-59; PMID:19455703; http://dx.doi.org/10.1002/gcc.20679
  • Thanasoula M, Escandell JM, Martinez P, Badie S, Muñoz P, Blasco MA, Tarsounas M. p53 prevents entry into mitosis with uncapped telomeres. Curr Biol 2010; 20:521-6; PMID:20226664; http://dx.doi.org/10.1016/j.cub.2010.01.046
  • Williams RS, Moncalian G, Williams JS, Yamada Y, Limbo O, Shin DS, Groocock LM, Cahill D, Hitomi C, Guenther G, et al. Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell 2008; 135:97-109; PMID:18854158; http://dx.doi.org/10.1016/j.cell.2008.08.017
  • Schultz LB, Chehab NH, Malikzay A, Halazonetis TD. P53 binding protein 1 (53bp1) is an early participant in the cellular response to DNA double-strand breaks. J Cell Biol 2000; 151:1381-90; PMID:11134068; http://dx.doi.org/10.1083/jcb.151.7.1381
  • Jullien D, Vagnarelli P, Earnshaw WC, Adachi Y. Kinetochore localisation of the DNA damage response component 53BP1 during mitosis. J Cell Sci 2002; 115:71-9; PMID:11801725
  • Nelson G, Buhmann M, von Zglinicki T. DNA damage foci in mitosis are devoid of 53BP1. Cell Cycle 2009; 8:3379-83; PMID:19806024; http://dx.doi.org/10.4161/cc.8.20.9857
  • Deckbar D, Birraux J, Krempler A, Tchouandong L, Beucher A, Walker S, Stiff T, Jeggo P, Löbrich M. Chromosome breakage after G2 checkpoint release. J Cell Biol 2007; 176:749-55; PMID:17353355; http://dx.doi.org/10.1083/jcb.200612047
  • Li P, Hou M, Lou F, Björkholm M, Xu D. Telomere dysfunction induced by chemotherapeutic agents and radiation in normal human cells. Int J Biochem Cell Biol 2012; 44:1531-40; PMID:22728163; http://dx.doi.org/10.1016/j.biocel.2012.06.020
  • Cesare AJ, Kaul Z, Cohen SB, Napier CE, Pickett HA, Neumann AA, Reddel RR. Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions. Nat Struct Mol Biol 2009; 16:1244-51; PMID:19935685; http://dx.doi.org/10.1038/nsmb.1725
  • Cesare Anthony J, Hayashi Makoto T, Crabbe L, Karlseder J. The telomere deprotection response is functionally distinct from the genomic DNA damage response. Mol Cell 2013; 51:141-55; PMID:23850488; http://dx.doi.org/10.1016/j.molcel.2013.06.006
  • Jullien L, Mestre M, Roux P, Gire V. Eroded human telomeres are more prone to remain uncapped and to trigger a G2 checkpoint response. Nucl Acids Res 2013; 41:900-11; PMID:23193277; http://dx.doi.org/10.1093/nar/gks1121
  • Seo J, Kim K, Chang D-Y, Kang H-B, Shin E-C, Kwon J, Choi JK. Genome-wide reorganization of histone H2AX toward particular fragile sites on cell activation. Nucl Acids Res 2014; 42:1016-25; PMID:24163101; http://dx.doi.org/10.1093/nar/gkt951
  • Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, de Lange T. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 2009; 138:90-103; PMID:19596237; http://dx.doi.org/10.1016/j.cell.2009.06.021
  • MacPhail SH, Banáth JP, Yu Y, Chu E, Olive PL. Cell cycle-dependent expression of phosphorylated histone H2AX: Reduced expression in unirradiated but not X-irradiated G1-phase cells. Radiat Res 2003:759-67; PMID:12751958; http://dx.doi.org/10.1667/RR3003
  • Tu W-Z, Li B, Huang B, Wang Y, Liu X-D, Guan H, Zhang SM, Tang Y, Rang WQ, Zhou PK, et al. γH2AX foci formation in the absence of DNA damage: Mitotic H2AX phosphorylation is mediated by the DNA-PKcs/CHK2 pathway. FEBS Lett 2013; 587:3437-43; PMID:24021642; http://dx.doi.org/10.1016/j.febslet.2013.08.028
  • Zhang W, Peng G, Lin S-Y, Zhang P. DNA damage response is suppressed by the high cyclin-dependent kinase 1 activity in mitotic mammalian cells. J Biol Chem 2011; 286:35899-905; PMID:21878640; http://dx.doi.org/10.1074/jbc.M111.267690
  • Giunta S, Belotserkovskaya R, Jackson SP. DNA damage signaling in response to double-strand breaks during mitosis. J Cell Biol 2010; 190:197-207; PMID:20660628; http://dx.doi.org/10.1083/jcb.200911156
  • Williams RS, Williams JS, Tainera JA. Mre11–Rad50–Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin template. Biochem Cell Biol 2007; 85:509-20; PMID:17713585; http://dx.doi.org/10.1139/O07-069
  • Lee J-H, Paull TT. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 2005; 308:551-4; PMID:15790808; http://dx.doi.org/10.1126/science.1108297
  • Uziel T, Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 2003; 22:5612-21; PMID:14532133; http://dx.doi.org/10.1093/emboj/cdg541
  • Jeppesen P. Immunofluorescence in cytogenetic analysis: method and applications. Genet Mol Biol 2000; 23 1107-14; http://dx.doi.org/10.1590/S1415-47572000000400059

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