{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:41:27Z","timestamp":1791193287523,"version":"4.1.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,12,9]]},"abstract":"<jats:p>\n                    We recently have shown that mice deficient for the 86-kDa component (Ku80) of the DNA-dependent protein kinase exhibit growth retardation and a profound deficiency in V(D)J (variable, diversity, and joining) recombination. These defects may be related to abnormalities in DNA metabolism that arise from the inability of\n                    <jats:italic>Ku80<\/jats:italic>\n                    mutant cells to process DNA double-strand breaks. To further characterize the role of Ku80 in DNA double-strand break repair, we have generated embryonic stem cells and pre-B cells and examined their response to ionizing radiation.\n                    <jats:italic>Ku80<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    embryonic stem cells are more sensitive than controls to \u03b3-irradiation, and pre-B cells derived from\n                    <jats:italic>Ku80<\/jats:italic>\n                    mutant mice display enhanced spontaneous and \u03b3-ray-induced apoptosis. We then determined the effects of ionizing radiation on the survival, growth, and lymphocyte development in\n                    <jats:italic>Ku80<\/jats:italic>\n                    -deficient mice.\n                    <jats:italic>Ku80<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice display a hypersensitivity to \u03b3-irradiation, characterized by loss of hair pigmentation, severe injury to the gastrointestinal tract, and enhanced mortality. Exposure of newborn\n                    <jats:italic>Ku80<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice to sublethal doses of ionizing radiation enhances their growth retardation and results in the induction of T cell-specific differentiation. However, unlike severe combined immunodeficient mice, radiation-induced T cell development in\n                    <jats:italic>Ku80<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice is not accompanied by extensive thymocyte proliferation. The response of\n                    <jats:italic>Ku80<\/jats:italic>\n                    -deficient cell lines and mice to DNA-damaging agents provides important insights into the role of Ku80 in growth regulation, lymphocyte development, and DNA repair.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.25.13588","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"13588-13593","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":153,"title":["Hypersensitivity of\n                    <i>Ku80<\/i>\n                    -deficient cell lines and mice to DNA damage: The effects of ionizing radiation on growth, survival, and\u2009development"],"prefix":"10.1073","volume":"94","author":[{"given":"Andr\u00e9","family":"Nussenzweig","sequence":"first","affiliation":[{"name":"Departments of Medical Physics and Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Laboratory Animal Research Center, The Rockefeller University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Sokol","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics and Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Laboratory Animal Research Center, The Rockefeller University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Burgman","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics and Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Laboratory Animal Research Center, The Rockefeller University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligeng","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics and Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Laboratory Animal Research Center, The Rockefeller University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria C.","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics and Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Laboratory Animal Research Center, The Rockefeller University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,12,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950171108"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)89121-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90135-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(93)90144-C"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.18.8343"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8469973"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7939667"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/382551a0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7855601"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90360-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.15.8076"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.6.921"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(95)80085-9"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.09.040191.001543"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3171"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.10.5507"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10285"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80111-7"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.143.6.1453"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990130802"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80085-6"},{"key":"e_1_3_3_22_2","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.4049\/jimmunol.153.3.1004","volume":"153","author":"Murphy 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