{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:13:17Z","timestamp":1791407597835,"version":"4.3.3"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5569","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2002,5,3]]},"abstract":"<jats:p>\n                    Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.\n                  <\/jats:p>","DOI":"10.1126\/science.1069398","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:54:32Z","timestamp":1027749272000},"page":"922-927","source":"Crossref","is-referenced-by-count":1208,"title":["Genomic Instability in Mice Lacking Histone H2AX"],"prefix":"10.1126","volume":"296","author":[{"given":"Arkady","family":"Celeste","sequence":"first","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Petersen","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Romanienko","sequence":"additional","affiliation":[{"name":"Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Fernandez-Capetillo","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua Tang","family":"Chen","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga A.","family":"Sedelnikova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Reina-San-Martin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, Howard Hughes Medical Institute, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Coppola","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, NIH, Frederick, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Meffre","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, Howard Hughes Medical Institute, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Difilippantonio","sequence":"additional","affiliation":[{"name":"Genetics Department, National Cancer Institute, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Redon","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duane R.","family":"Pilch","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Olaru","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 13-01, Baltimore, MD 21201, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Eckhaus","sequence":"additional","affiliation":[{"name":"Veterinary Resources Program, National Center for Research Resources, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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Sonoda et al. Mol. Cell. Biol. 19 5166 (1999).","DOI":"10.1128\/MCB.19.7.5166"},{"key":"e_1_3_1_33_2","doi-asserted-by":"crossref","unstructured":"J. Essers et al. Cell 89 195 (1997).","DOI":"10.1016\/S0092-8674(00)80199-3"},{"key":"e_1_3_1_34_2","unstructured":"R. S. Maser et al. Mol. Cell. Biol. 21 6006 (2001)."},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00019-7"},{"key":"e_1_3_1_36_2","unstructured":"We thank J. Chen S. Ganesan D. Livingston P. Moens B. Spyropoulos and C. Heyting for antisera; T. Ried X. Tai J. Zhu S. Kerns S. Gonzalez K. Hathcock and M. Krulack for assistance; R. Kanaar for gene-targeting constructs; R. Schroff and M. Lichten for sharing unpublished data; and A. Singer and M. Lichten for comments on the manuscript and helpful discussions. This work was supported in part by grants from the NIH and the Leukemia Society (M.C.N.). 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