- McKinnon, P. J. & Caldecott, K. W. DNA strand break repair and human genetic disease. Annu. Rev. Genomics Hum. Genet. 8, 37–55 (2007).
Article CAS PubMed Google Scholar
- Jeggo, P. A. & Lobrich, M. DNA double-strand breaks: their cellular and clinical impact? Oncogene 26, 7717–7719 (2007).
Article CAS PubMed Google Scholar
- Hakem, R. DNA-damage repair; the good, the bad, and the ugly. EMBO J. 27, 589–605 (2008).
Article CAS PubMed PubMed Central Google Scholar
- O'Driscoll, M., Gennery, A. R., Seidel, J., Concannon, P. & Jeggo, P. A. An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR–Seckel syndrome. DNA Repair (Amst.) 3, 1227–1235 (2004).
Article CAS Google Scholar
- Rogakou, E. P., Boon, C., Redon, C. & Bonner, W. M. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J. Cell Biol. 146, 905–916 (1999).
Article CAS PubMed PubMed Central Google Scholar
- Helleday, T., Petermann, E., Lundin, C., Hodgson, B. & Sharma, R. A. DNA repair pathways as targets for cancer therapy. Nature Rev. Cancer 8, 193–204 (2008).
Article CAS Google Scholar
- Takahashi, A. & Ohnishi, T. Does γH2AX foci formation depend on the presence of DNA double strand breaks? Cancer Lett. 229, 171–179 (2005).
Article CAS PubMed Google Scholar
- Sedelnikova, O. A., Pilch, D. R., Redon, C. & Bonner, W. M. Histone H2AX in DNA damage and repair. Cancer Biol. Ther. 2, 233–235 (2003).
Article CAS PubMed Google Scholar
- Sedelnikova, O. A. & Bonner, W. M. γH2AX in cancer cells: a potential biomarker for cancer diagnostics, prediction and recurrence. Cell Cycle 5, 2909–2913 (2006).
Article CAS PubMed Google Scholar
- Kinner, A., Wu, W., Staudt, C. & Iliakis, G. γH2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res. 36, 5678–5694 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Wang, B. & Elledge, S. J. Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc. Natl Acad. Sci. USA 104, 20759–20763 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Kolas, N. K. et al. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318, 1637–1640 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Bartova, E., Krejci, J., Harnicarova, A., Galiova, G. & Kozubek, S. Histone modifications and nuclear architecture: a review. J. Histochem. Cytochem. 56, 711–721 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S. & Bonner, W. M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273, 5858–5868 (1998).
Article CAS PubMed Google Scholar
- Levine, B. J., Chodchoy, N., Marzluff, W. F. & Skoultchi, A. I. Coupling of replication type histone mRNA levels to DNA synthesis requires the stem-loop sequence at the 3′ end of the mRNA. Proc. Natl Acad. Sci. USA 84, 6189–6193 (1987).
Article CAS PubMed PubMed Central Google Scholar
- Wu, R. S. & Bonner, W. M. Separation of basal histone synthesis from S-phase histone synthesis in dividing cells. Cell 27, 321–330 (1981).
Article CAS PubMed Google Scholar
- Mannironi, C., Bonner, W. M. & Hatch, C. L. H2A.X. a histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3' processing signals. Nucleic Acids Res. 17, 9113–9126 (1989).
Article CAS PubMed PubMed Central Google Scholar
- Mailand, N. et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131, 887–900 (2007).
Article CAS PubMed Google Scholar
- Kruhlak, M. J. et al. Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks. J. Cell Biol. 172, 823–834 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Paull, T. T. et al. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr. Biol. 10, 886–895 (2000).
Article CAS PubMed Google Scholar
- Shroff, R. et al. Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr. Biol. 14, 1703–1711 (2004).
Article CAS PubMed PubMed Central Google Scholar
- Redon, C. et al. Yeast histone 2A serine 129 is essential for the efficient repair of checkpoint-blind DNA damage. EMBO Rep. 4, 678–684 (2003).
Article CAS PubMed PubMed Central Google Scholar
- Mirzayans, R., Severin, D. & Murray, D. Relationship between DNA double-strand break rejoining and cell survival after exposure to ionizing radiation in human fibroblast strains with differing ATM/p53 status: implications for evaluation of clinical radiosensitivity. Int. J. Radiat. Oncol. Biol. Phys. 66, 1498–1505 (2006).
Article CAS PubMed Google Scholar
- Chowdhury, D. et al. γH2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol. Cell 20, 801–809 (2005).
Article CAS PubMed Google Scholar
- Keogh, M. C. et al. A phosphatase complex that dephosphorylates γH2AX regulates DNA damage checkpoint recovery. Nature 439, 497–501 (2006).
Article CAS PubMed Google Scholar
- Chowdhury, D. et al. A PP4-phosphatase complex dephosphorylates γH2AX generated during DNA replication. Mol. Cell 31, 33–46 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Nakada, S., Chen, G. I., Gingras, A. C. & Durocher, D. PP4 is a γH2AX phosphatase required for recovery from the DNA damage checkpoint. EMBO Rep. 9, 1019–1026 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Downs, J. A. et al. Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol. Cell 16, 979–990 (2004).
Article CAS PubMed Google Scholar
- Morrison, A. J. et al. INO80 and γH2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell 119, 767–775 (2004).
Article CAS PubMed Google Scholar
- Kusch, T. et al. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science 306, 2084–2087 (2004).
Article CAS PubMed Google Scholar
- van Attikum, H., Fritsch, O., Hohn, B. & Gasser, S. M. Recruitment of the INO80 complex by H2A phosphorylation links ATP-dependent chromatin remodeling with DNA double-strand break repair. Cell 119, 777–788 (2004).
Article CAS PubMed Google Scholar
- van Attikum, H. & Gasser, S. M. ATP-dependent chromatin remodeling and DNA double-strand break repair. Cell Cycle 4, 1011–1014 (2005).
Article CAS PubMed Google Scholar
- Stiff, T. et al. ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J. 25, 5775–5782 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Marti, T. M., Hefner, E., Feeney, L., Natale, V. & Cleaver, J. E. H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks. Proc. Natl Acad. Sci. USA 103, 9891–9896 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Hanasoge, S. & Ljungman, M. H2AX phosphorylation after UV-irradiation is triggered by DNA repair intermediates and is mediated by the ATR kinase. Carcinogenesis 28, 2298–2304 (2007).
Article CAS PubMed Google Scholar
- Bassing, C. H. et al. Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX. Proc. Natl Acad. Sci. USA 99, 8173–8178 (2002).
Article CAS PubMed PubMed Central Google Scholar
- Bassing, C. H. et al. Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 114, 359–370 (2003).
Article CAS PubMed Google Scholar
- Thirman, M. J. et al. Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N. Engl. J. Med. 329, 909–914 (1993).
Article CAS PubMed Google Scholar
- Parikh, R. A. et al. Loss of distal 11q is associated with DNA repair deficiency and reduced sensitivity to ionizing radiation in head and neck squamous cell carcinoma. Genes Chromosomes Cancer 46, 761–775 (2007).
Article CAS PubMed Google Scholar
- Srivastava, N., Gochhait, S., Gupta, P. & Bamezai, R. N. Copy number alterations of the H2AFX gene in sporadic breast cancer patients. Cancer Genet. Cytogenet. 180, 121–128 (2008 ).
Article CAS PubMed Google Scholar
- Novik, K. L. et al. Genetic variation in H2AFX contributes to risk of non-Hodgkin lymphoma. Cancer Epidemiol. Biomarkers Prev. 16, 1098–1106 (2007).
Article CAS PubMed Google Scholar
- Liu, Y. et al. Histone H2AX is a mediator of gastrointestinal stromal tumor cell apoptosis following treatment with imatinib mesylate. Cancer Res. 67, 2685–2692 (2007).
Article CAS PubMed Google Scholar
- Celeste, A. et al. Genomic instability in mice lacking histone H2AX. Science 296, 922–927 (2002).
Article CAS PubMed PubMed Central Google Scholar
- Celeste, A. et al. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114, 371–383 (2003).
Article CAS PubMed PubMed Central Google Scholar
- Goodarzi, A. A. et al. ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol. Cell 31, 167–177 (2008).
Article CAS PubMed Google Scholar
- Ghiassi-nejad, M., Mortazavi, S. M., Cameron, J. R., Niroomand-rad, A. & Karam, P. A. Very high background radiation areas of Ramsar, Iran: preliminary biological studies. Health Phys. 82, 87–93 (2002).
Article CAS PubMed Google Scholar
- Desai, N., Durante, M., Lin, Z. W., Cucinotta, F. & Wu, H. High LET-induced H2AX phosphorylation around the Bragg curve. Adv. Space Res. 35, 236–242 (2005).
Article CAS PubMed Google Scholar
- Brenner, D. J. & Ward, J. F. Constraints on energy deposition and target size of multiply damaged sites associated with DNA double-strand breaks. Int. J. Radiat. Biol. 61, 737–748 (1992).
Article CAS PubMed Google Scholar
- Hagen, U. Mechanisms of induction and repair of DNA double-strand breaks by ionizing radiation: some contradictions. Radiat. Environ. Biophys. 33, 45–61 (1994).
Article CAS PubMed Google Scholar
- Bonner, W. M. Phenomena leading to cell survival values which deviate from linear-quadratic models. Mutat. Res. 568, 33–39 (2004).
Article CAS PubMed Google Scholar
- Kielbassa, C., Roza, L. & Epe, B. Wavelength dependence of oxidative DNA damage induced by UV and visible light. Carcinogenesis 18, 811–816 (1997).
Article CAS PubMed Google Scholar
- Klaunig, J. E. & Kamendulis, L. M. The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 44, 239–267 (2004).
Article CAS PubMed Google Scholar
- Tanaka, T., Halicka, H. D., Huang, X., Traganos, F. & Darzynkiewicz, Z. Constitutive histone H2AX phosphorylation and ATM activation, the reporters of DNA damage by endogenous oxidants. Cell Cycle 5, 1940–1945 (2006).
Article CAS PubMed Google Scholar
- Hussain, S. P., Hofseth, L. J. & Harris, C. C. Radical causes of cancer. Nature Rev. Cancer 3, 276–285 (2003).
Article CAS Google Scholar
- Federico, A., Morgillo, F., Tuccillo, C., Ciardiello, F. & Loguercio, C. Chronic inflammation and oxidative stress in human carcinogenesis. Int. J. Cancer 121, 2381–2386 (2007).
Article CAS PubMed Google Scholar
- Burhans, W. C. & Weinberger, M. DNA replication stress, genome instability and aging. Nucleic Acids Res. 35, 7545–7556 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Sobol, R. W. et al. Base excision repair intermediates induce p53-independent cytotoxic and genotoxic responses. J. Biol. Chem. 278, 39951–39959 (2003).
Article CAS PubMed Google Scholar
- Pommier, Y. Topoisomerase I inhibitors: camptothecins and beyond. Nature Rev. Cancer 6, 789–802 (2006).
Article CAS Google Scholar
- Yamashita, Y. et al. Induction of mammalian DNA topoisomerase I mediated DNA cleavage by antitumor indolocarbazole derivatives. Biochemistry 31, 12069–12075 (1992).
Article CAS PubMed Google Scholar
- Pourquier, P. & Pommier, Y. Topoisomerase I-mediated DNA damage. Adv. Cancer Res. 80, 189–216 (2001).
Article CAS PubMed Google Scholar
- McClendon, A. K. & Osheroff, N. DNA topoisomerase II, genotoxicity, and cancer. Mutat. Res. 623, 83–97 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Fortune, J. M. & Osheroff, N. Topoisomerase II as a target for anticancer drugs: when enzymes stop being nice. Prog. Nucleic Acid Res. Mol. Biol. 64, 221–253 (2000).
Article CAS PubMed Google Scholar
- Guirouilh-Barbat, J., Redon, C. & Pommier, Y. Transcription-coupled DNA double-strand breaks are mediated via the nucleotide excision repair and the Mre11–Rad50–Nbs1 complex. Mol. Biol. Cell 19, 3969–3981 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Wilson, D. M. 3rd & Bohr, V. A. The mechanics of base excision repair, and its relationship to aging and disease. DNA Repair (Amst.) 6, 544–559 (2007).
Article CAS Google Scholar
- Nowosielska, A. & Marinus, M. G. DNA mismatch repair-induced double-strand breaks. DNA Repair (Amst.) 7, 48–56 (2008).
Article CAS Google Scholar
- McCulloch, S. D. & Kunkel, T. A. The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res. 18, 148–161 (2008).
Article CAS PubMed Google Scholar
- Kraemer, K. H. et al. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype–phenotype relationship. Neuroscience 145, 1388–1396 (2007).
Article CAS PubMed Google Scholar
- Andressoo, J. O., Hoeijmakers, J. H. & Mitchell, J. R. Nucleotide excision repair disorders and the balance between cancer and aging. Cell Cycle 5, 2886–2888 (2006).
Article CAS PubMed Google Scholar
- Cheadle, J. P. & Sampson, J. R. Exposing the MYtH about base excision repair and human inherited disease. Hum. Mol. Genet. 12, R159–R165 (2003).
Article CAS PubMed Google Scholar
- Rustgi, A. K. The genetics of hereditary colon cancer. Genes Dev. 21, 2525–2538 (2007).
Article CAS PubMed Google Scholar
- Campisi, J. & d'Adda di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nature Rev. Mol. Cell Biol. 8, 729–740 (2007).
Article CAS Google Scholar
- d'Adda di Fagagna, F. Living on a break: cellular senescence as a DNA-damage response. Nature Rev. Cancer 8, 512–522 (2008).
Article CAS Google Scholar
- Takai, H., Smogorzewska, A. & de Lange, T. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13, 1549–1556 (2003).
Article CAS PubMed Google Scholar
- Nakamura, A. J. et al. Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence. Epigenet. Chromatin (in the press).
- Deng, Y., Chan, S. S. & Chang, S. Telomere dysfunction and tumour suppression: the senescence connection. Nature Rev. Cancer 8, 450–458 (2008).
Article CAS Google Scholar
- Edry, E. & Melamed, D. Class switch recombination: a friend and a foe. Clin. Immunol. 123, 244–251 (2007).
Article CAS PubMed Google Scholar
- Soulas-Sprauel, P. et al. V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining. Oncogene 26, 7780–7791 (2007).
Article CAS PubMed Google Scholar
- Mahadevaiah, S. K. et al. Recombinational DNA double-strand breaks in mice precede synapsis. Nature Genet. 27, 271–276 (2001).
Article CAS PubMed Google Scholar
- Fernandez-Capetillo, O. et al. H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev. Cell 4, 497–508 (2003).
Article CAS PubMed Google Scholar
- Rogakou, E. P., Nieves-Neira, W., Boon, C., Pommier, Y. & Bonner, W. M. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J. Biol. Chem. 275, 9390–9395 (2000).
Article CAS PubMed Google Scholar
- Samejima, K. & Earnshaw, W. C. Trashing the genome: the role of nucleases during apoptosis. Nature Rev. Mol. Cell Biol. 6, 677–688 (2005).
Article CAS Google Scholar
- Tarakanova, V. L. et al. Gammaherpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication. Cell Host Microbe 1, 275–286 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Bartkova, J. et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434, 864–870 (2005).
Article CAS PubMed Google Scholar
- Gorgoulis, V. G. et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434, 907–913 (2005).
Article CAS PubMed Google Scholar
- Sedelnikova, O. A., Rogakou, E. P., Panyutin, I. G. & Bonner, W. M. Quantitative detection of 125IdU-induced DNA double-strand breaks with γ-H2AX antibody. Radiat. Res. 158, 486–492 (2002).
Article CAS PubMed Google Scholar
- 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. Natl Acad. Sci. USA 100, 5057–5062 (2003).
Article CAS PubMed PubMed Central Google Scholar
- Sedelnikova, O. A. et al. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nature Cell Biol. 6, 168–170 (2004).
Article CAS PubMed Google Scholar
- Lobrich, M. et al. In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. Proc. Natl Acad. Sci. USA 102, 8984–8989 (2005).
Article PubMed CAS PubMed Central Google Scholar
- Qvarnstrom, O. F., Simonsson, M., Johansson, K. A., Nyman, J. & Turesson, I. DNA double strand break quantification in skin biopsies. Radiother. Oncol. 72, 311–317 (2004).
Article PubMed CAS Google Scholar
- Huang, X., Halicka, H. D. & Darzynkiewicz, Z. Detection of histone H2AX phosphorylation on Ser-139 as an indicator of DNA damage (DNA double-strand breaks). Curr. Protoc. Cytom. Chapter 7 Unit 7.27 (2004).
- Tanaka, T. et al. Cytometry of ATM activation and histone H2AX phosphorylation to estimate extent of DNA damage induced by exogenous agents. Cytometry A 71, 641–648 (2007).
Google Scholar
- Olive, P. L. & Banath, J. P. Phosphorylation of histone H2AX as a measure of radiosensitivity. Int. J. Radiat. Oncol. Biol. Phys. 58, 331–335 (2004).
Article CAS PubMed Google Scholar
- Rothkamm, K., Balroop, S., Shekhdar, J., Fernie, P. & Goh, V. Leukocyte DNA damage after multi-detector row CT: a quantitative biomarker of low-level radiation exposure. Radiology 242, 244–251 (2007).
Article PubMed Google Scholar
- Sedelnikova, O. A. et al. DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Cancer Res. 67, 4295–4302 (2007).
Article CAS PubMed Google Scholar
- Sedelnikova, O. A. et al. Delayed kinetics of DNA double-strand break processing in normal and pathological aging. Aging Cell 7, 89–100 (2008).
Article CAS PubMed Google Scholar
- Takagi, K. et al. Novel E-ring camptothecin keto analogues (S38809 and S39625) are stable, potent, and selective topoisomerase I inhibitors without being substrates of drug efflux transporters. Mol. Cancer Ther. 6, 3229–3238 (2007).
Article CAS PubMed Google Scholar
- Albert, J. M. et al. Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin. Cancer Res. 13, 3033–3042 (2007).
Article CAS PubMed Google Scholar
- Rao, V. A., Agama, K., Holbeck, S. & Pommier, Y. Batracylin (NSC 320846), a dual inhibitor of DNA topoisomerases I and II induces histone γ-H2AX as a biomarker of DNA damage. Cancer Res. 67, 9971–9979 (2007).
Article CAS PubMed Google Scholar
- Shimura, T. et al. Bloom's syndrome helicase and Mus81 are required to induce transient double-strand DNA breaks in response to DNA replication stress. J. Mol. Biol. 375, 1152–1164 (2008).
Article CAS PubMed Google Scholar
- MacPhail, S. H., Banath, J. P., Yu, Y., Chu, E. & Olive, P. L. Cell cycle-dependent expression of phosphorylated histone H2AX: reduced expression in unirradiated but not X-irradiated G1-phase cells. Radiat. Res. 159, 759–767 (2003).
Article CAS PubMed Google Scholar
- Ismail, I. H., Wadhra, T. I. & Hammarsten, O. An optimized method for detecting γ-H2AX in blood cells reveals a significant interindividual variation in the γ-H2AX response among humans. Nucleic Acids Res. 35, e36 (2007).
Article PubMed PubMed Central CAS Google Scholar
- Olive, P. L., Banath, J. P. & Keyes, M. Residual γH2AX after irradiation of human lymphocytes and monocytes in vitro and its relation to late effects after prostate brachytherapy. Radiother Oncol. 86, 336–346 (2008).
Article CAS PubMed Google Scholar
- Ha, L., Ceryak, S. & Patierno, S. R. Generation of S. phase-dependent DNA double-strand breaks by Cr(VI) exposure: involvement of ATM in Cr(VI) induction of γ-H2AX. Carcinogenesis 25, 2265–2274 (2004).
Article CAS PubMed Google Scholar
- Furuta, T. et al. Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J. Biol. Chem. 278, 20303–20312 (2003).
Article CAS PubMed Google Scholar
- Celeste, A. et al. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nature Cell Biol. 5, 675–679 (2003).
Article CAS PubMed Google Scholar
- Koturbash, I. et al. Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo. Int. J. Radiat. Oncol. Biol. Phys. 66, 327–330 (2006).
Article CAS PubMed Google Scholar
- Xie, A. et al. Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair. Mol. Cell 28, 1045–1057 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Joubert, A. et al. DNA double-strand break repair defects in syndromes associated with acute radiation response: at least two different assays to predict intrinsic radiosensitivity? Int. J. Radiat. Biol. 84, 107–125 (2008).
Article CAS PubMed Google Scholar
- Iwabuchi, K. et al. Potential role for 53BP1 in DNA end-joining repair through direct interaction with DNA. J. Biol. Chem. 278, 36487–36495 (2003).
Article CAS PubMed Google Scholar
- Jeyapalan, J. C., Ferreira, M., Sedivy, J. M. & Herbig, U. Accumulation of senescent cells in mitotic tissue of aging primates. Mech. Ageing Dev. 128, 36–44 (2007).
Article CAS PubMed Google Scholar
- Porcedda, P. et al. Impaired elimination of DNA double-strand break-containing lymphocytes in ataxia telangiectasia and Nijmegen breakage syndrome. DNA Repair (Amst.) 5, 904–913 (2006).
Article CAS Google Scholar
- Tanaka, T., Kajstura, M., Halicka, H. D., Traganos, F. & Darzynkiewicz, Z. Constitutive histone H2AX phosphorylation and ATM activation are strongly amplified during mitogenic stimulation of lymphocytes. Cell Prolif. 40, 1–13 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Halazonetis, T. D., Gorgoulis, V. G. & Bartek, J. An oncogene-induced DNA damage model for cancer development. Science 319, 1352–1355 (2008).
Article CAS PubMed Google Scholar
- Fagerholm, R. et al. NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nature Genet. 40, 844–853 (2008).
Article CAS PubMed Google Scholar
- Yu, T., MacPhail, S. H., Banath, J. P., Klokov, D. & Olive, P. L. Endogenous expression of phosphorylated histone H2AX in tumors in relation to DNA double-strand breaks and genomic instability. DNA Repair (Amst.) 5, 935–946 (2006).
Article CAS Google Scholar
- Wasco, M. J. & Pu, R. T. Utility of antiphosphorylated H2AX antibody (γ-H2AX) in diagnosing metastatic renal cell carcinoma. Appl. Immunohistochem. Mol. Morphol. 16, 349–356 (2008).
Article CAS PubMed Google Scholar
- Lakatos, P. L. & Lakatos, L. Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies. World J. Gastroenterol. 14, 3937–3947 (2008).
Article PubMed PubMed Central Google Scholar
- Risques, R. A. et al. Ulcerative colitis is a disease of accelerated colon aging: evidence from telomere attrition and DNA damage. Gastroenterology 135, 410–418 (2008).
Article CAS PubMed Google Scholar
- Porcedda, P. et al. A rapid flow cytometry test based on histone H2AX phosphorylation for the sensitive and specific diagnosis of ataxia telangiectasia. Cytometry A 73, 508–516 (2008).
Article PubMed Google Scholar
- Riballo, E. et al. A pathway of double-strand break rejoining dependent upon, A. T. M., Artemis, and proteins locating to γ-H2AX foci. Mol. Cell 16, 715–724 (2004).
Article CAS PubMed Google Scholar
- Geisel, D., Heverhagen, J. T., Kalinowski, M. & Wagner, H. J. DNA double-strand breaks after percutaneous transluminal angioplasty. Radiology 248, 852–859 (2008).
Article PubMed Google Scholar
- Sak, A. et al. γ-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose-distribution, irradiated site and time from start of treatment. Int. J. Radiat. Biol. 83, 639–652 (2007).
Article CAS PubMed Google Scholar
- Childs, S. & Ling, V. The MDR superfamily of genes and its biological implications. Important Adv. Oncol. 21–36 (1994).
- Kummar, S. et al. Compressing drug development timelines in oncology using phase '0' trials. Nature Rev. Cancer 7, 131–139 (2007).
Article CAS Google Scholar
- Karp, J. E. et al. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias. Blood 110, 1762–1769 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Yauk, C. et al. Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location. Proc. Natl Acad. Sci. USA 105, 605–610 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Rekhadevi, P. V. et al. Genotoxicity assessment in oncology nurses handling anti-neoplastic drugs. Mutagenesis 22, 395–401 (2007).
Article CAS PubMed Google Scholar
- Markova, E., Hillert, L., Malmgren, L., Persson, B. R. & Belyaev, I. Y. Microwaves from GSM mobile telephones affect 53BP1 and γ-H2AX foci in human lymphocytes from hypersensitive and healthy persons. Environ. Health Perspect. 113, 1172–1177 (2005).
Article CAS PubMed PubMed Central Google Scholar
- Briviba, K. et al. Effect of consumption of organically and conventionally produced apples on antioxidant activity and DNA damage in humans. J. Agric. Food Chem. 55, 7716–7721 (2007).
Article CAS PubMed Google Scholar
- Markova, E., Schultz, N. & Belyaev, I. Y. Kinetics and dose–response of residual 53BP1/ γ-H2AX foci: co-localization, relationship with DSB repair and clonogenic survival. Int. J. Radiat. Biol. 83, 319–329 (2007).
Article CAS PubMed Google Scholar
- McManus, K. J. & Hendzel, M. J. ATM-dependent DNA damage-independent mitotic phosphorylation of H2AX in normally growing mammalian cells. Mol. Biol. Cell 16, 5013–5025 (2005).
Article CAS PubMed PubMed Central Google Scholar
- Ward, I. M. & Chen, J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J. Biol. Chem. 276, 47759–47762 (2001).
Article CAS PubMed Google Scholar
- Ichijima, Y. et al. Phosphorylation of histone H2AX at M phase in human cells without DNA damage response. Biochem. Biophys. Res. Commun. 336, 807–812 (2005).
Article CAS PubMed Google Scholar
- Jeffers, L. J., Coull, B. J., Stack, S. J. & Morrison, C. G. Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization. Oncogene 27, 139–144 (2008).
Article CAS PubMed Google Scholar
- Chicheportiche, A., Bernardino-Sgherri, J., de Massy, B. & Dutrillaux, B. Characterization of Spo11-dependent and independent phospho-H2AX foci during meiotic prophase I in the male mouse. J. Cell Sci. 120, 1733–1742 (2007).
Article CAS PubMed Google Scholar
- Daniel, R. et al. Histone H2AX is phosphorylated at sites of retroviral DNA integration but is dispensable for postintegration repair. J. Biol. Chem. 279, 45810–45814 (2004).
Article CAS PubMed Google Scholar
- Stiff, T. et al. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 64, 2390–2396 (2004).
Article CAS PubMed Google Scholar
- Stucki, M. & Jackson, S. P. γH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes. DNA Repair (Amst.) 5, 534–543 (2006).
Article CAS Google Scholar
- Kobayashi, J. et al. NBS1 localizes to γ-H2AX foci through interaction with the FHA/BRCT domain. Curr. Biol. 12, 1846–1851 (2002).
Article CAS PubMed Google Scholar
- di Masi, A. et al. The R215W mutation in NBS1 impairs γ-H2AX binding and affects DNA repair: molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage syndrome patients. Biochem. Biophys. Res. Commun. 369, 835–840 (2008).
Article CAS PubMed Google Scholar
- Lou, Z. et al. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell 21, 187–200 (2006).
Article CAS PubMed Google Scholar
- Wood, J. L., Singh, N., Mer, G. & Chen, J. MCPH1 functions in an H2AX-dependent but MDC1-independent pathway in response to DNA damage. J. Biol. Chem. 282, 35416–35423 (2007).
Article CAS PubMed Google Scholar
- Alderton, G. K. et al. Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. Nature Cell Biol. 8, 725–733 (2006).
Article CAS PubMed Google Scholar
- Chaplet, M., Rai, R., Jackson-Bernitsas, D., Li, K. & Lin, S. Y. BRIT1/MCPH1: a guardian of genome and an enemy of tumors. Cell Cycle 5, 2579–2583 (2006).
Article CAS PubMed Google Scholar
- Fernandez-Capetillo, O., Lee, A., Nussenzweig, M. & Nussenzweig, A. H2AX: the histone guardian of the genome. DNA Repair (Amst.) 3, 959–967 (2004).
Article CAS Google Scholar
- Ikura, T. et al. DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. Mol. Cell Biol. 27, 7028–7040 (2007).
Article CAS PubMed PubMed Central Google Scholar
- van Attikum, H., Fritsch, O. & Gasser, S. M. Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks. EMBO J. 26, 4113–4125 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Xie, A. et al. Control of sister chromatid recombination by histone H2AX. Mol. Cell 16, 1017–1025 (2004).
Article CAS PubMed Google Scholar
- Unal, E. et al. DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol. Cell 16, 991–1002 (2004).
Article PubMed Google Scholar
- Lu, C. et al. Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3. Mol. Cell 23, 121–132 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Lu, C. et al. Serum starvation induces H2AX phosphorylation to regulate apoptosis via p38 MAPK pathway. FEBS Lett. 582, 2703–2708 (2008).
Article CAS PubMed Google Scholar
- Marchetti, F., Coleman, M. A., Jones, I. M. & Wyrobek, A. J. Candidate protein biodosimeters of human exposure to ionizing radiation. Int. J. Radiat. Biol. 82, 605–639 (2006).
Article CAS PubMed Google Scholar
- Banath, J. P. & Olive, P. L. Expression of phosphorylated histone H2AX as a surrogate of cell killing by drugs that create DNA double-strand breaks. Cancer Res. 63, 4347–4350 (2003).
CAS PubMed Google Scholar
- Tomilin, N. V. et al. Visualization of focal nuclear sites of DNA repair synthesis induced by bleomycin in human cells. Radiat. Res. 156, 347–354 (2001).
Article CAS PubMed Google Scholar
- Antony, S. et al. Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance. Cancer Res. 67, 10397–10405 (2007).
Article CAS PubMed Google Scholar
- Olive, P. L., Banath, J. P. & Sinnott, L. T. Phosphorylated histone H2AX in spheroids, tumors, and tissues of mice exposed to etoposide and 3-amino-1,2,4-benzotriazine-1,3-dioxide. Cancer Res. 64, 5363–5369 (2004).
Article CAS PubMed Google Scholar
- Kurz, E. U. & Lees-Miller, S. P. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst.) 3, 889–900 (2004).
Article CAS Google Scholar
- Krynetskaia, N., Xie, H., Vucetic, S., Obradovic, Z. & Krynetskiy, E. High mobility group protein B1 is an activator of apoptotic response to antimetabolite drugs. Mol. Pharmacol. 73, 260–269 (2008).
Article CAS PubMed Google Scholar
- Ewald, B., Sampath, D. & Plunkett, W. H2AX phosphorylation marks gemcitabine-induced stalled replication forks and their collapse upon S-phase checkpoint abrogation. Mol. Cancer Ther. 6, 1239–1248 (2007).
Article CAS PubMed Google Scholar
- Kurose, A. et al. Effects of hydroxyurea and aphidicolin on phosphorylation of ataxia telangiectasia mutated on Ser 1981 and histone H2AX on Ser 139 in relation to cell cycle phase and induction of apoptosis. Cytometry A 69, 212–221 (2006).
Article PubMed Google Scholar
- Pabla, N., Huang, S., Mi, Q. S., Daniel, R. & Dong, Z. ATR–Chk2 signaling in p53 activation and DNA damage response during cisplatin-induced apoptosis. J. Biol. Chem. 283, 6572–6583 (2008).
Article CAS PubMed Google Scholar
- Mirzoeva, O. K., Kawaguchi, T. & Pieper, R. O. The Mre11/Rad50/Nbs1 complex interacts with the mismatch repair system and contributes to temozolomide-induced G2 arrest and cytotoxicity. Mol. Cancer Ther. 5, 2757–2766 (2006).
Article CAS PubMed Google Scholar
- Meng, L., Kohlhagen, G., Sausville, E. A. & Pommier, Y. DNA-protein crosslinks and replication-dependent histone H2AX phosphorylation induced by aminoflavone (NSC 686288), a novel anticancer agent active against breast cancer cells. Cancer Res. 65, 5337–5343 (2005).
Article CAS PubMed Google Scholar
- Kiziltepe, T. et al. 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. Mol. Cancer Ther. 6, 1718–1727 (2007).
Article CAS PubMed Google Scholar
- Munshi, A. et al. Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of γ-H2AX foci. Mol. Cancer Ther. 5, 1967–1974 (2006).
Article CAS PubMed Google Scholar
- Zhao, Y. et al. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 66, 5354–5362 (2006).
Article CAS PubMed Google Scholar
- Solier, S., Sordet, O., Kohn, K. W. & Pommier, Y. Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways. Mol. Cell Biol. (in the press).