{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:35:40Z","timestamp":1774085740192,"version":"3.50.1"},"reference-count":53,"publisher":"Proceedings of the National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,10,9]]},"abstract":"<jats:p>\n                    Chromatid catenation is actively monitored in human cells, with progression from G\n                    <jats:sub>2<\/jats:sub>\n                    to mitosis being inhibited when chromatids are insufficiently decatenated. Mitotic delay was quantified in normal and checkpoint-deficient human cells during treatment with ICRF-193, a topoisomerase II catalytic inhibitor that prevents chromatid decatenation without producing topoisomerase-associated DNA strand breaks. Ataxia telangiectasia (A-T) cells, defective in DNA damage checkpoints, showed normal mitotic delay when treated with ICRF-193. The mitotic delay in response to ICRF-193 was ablated in human fibroblasts expressing an ataxia telangiectasia mutated- and rad3-related (ATR) kinase-inactive\n                    <jats:italic>ATR<\/jats:italic>\n                    allele (ATR\n                    <jats:sup>ki<\/jats:sup>\n                    ). BRCA1-mutant HCC1937 cells also displayed a defect in ICRF-193-induced mitotic delay, which was corrected by expression of wild-type BRCA1. Phosphorylations of hCds1 or Chk1 and inhibition of Cdk1 kinase activity, which are elements of checkpoints associated with DNA damage or replication, did not occur during ICRF-193-induced mitotic delay. Over-expression of cyclin B1 containing a dominant nuclear localization signal, and inhibition of Crm1-mediated nuclear export, reversed ICRF-193-induced mitotic delay. In combination, these results imply that ATR and BRCA1 enforce the decatenation G\n                    <jats:sub>2<\/jats:sub>\n                    checkpoint, which may act to exclude cyclin B1\/Cdk1 complexes from the nucleus. Moreover, induction of ATR\n                    <jats:sup>ki<\/jats:sup>\n                    produced a 10-fold increase in chromosomal aberrations, further emphasizing the vital role for ATR in genetic stability.\n                  <\/jats:p>","DOI":"10.1073\/pnas.221430898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"12044-12049","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":152,"title":["The human decatenation checkpoint"],"prefix":"10.1073","volume":"98","author":[{"given":"Paula B.","family":"Deming","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Department of Cell Biology and Physiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63310; Growth Control and Cancer Group, National Institute of Environmental Health Science, Research Triangle Park, NC 27709; and School of Biomedical Science, University of Ulster, Coleraine BT521SA, Northern Ireland"}]},{"given":"Cheryl A.","family":"Cistulli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Department of Cell Biology and Physiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63310; Growth Control and Cancer Group, National Institute of Environmental Health Science, Research Triangle Park, NC 27709; and School of Biomedical Science, University of Ulster, Coleraine BT521SA, Northern Ireland"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Department of Cell Biology and Physiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63310; Growth Control and Cancer Group, National Institute of Environmental Health Science, Research Triangle Park, NC 27709; and School of Biomedical Science, University of Ulster, Coleraine BT521SA, Northern Ireland"}]},{"given":"Paul R.","family":"Graves","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Department of Cell Biology and Physiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63310; Growth Control and Cancer Group, National Institute of Environmental Health Science, Research Triangle Park, NC 27709; and School of Biomedical Science, University of Ulster, Coleraine BT521SA, Northern Ireland"}]},{"given":"Helen","family":"Piwnica-Worms","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Department of Cell Biology and Physiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63310; Growth Control and Cancer Group, National Institute of Environmental Health Science, Research Triangle Park, NC 27709; and School of Biomedical Science, University of Ulster, Coleraine BT521SA, Northern Ireland"}]},{"given":"Richard S.","family":"Paules","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Department of Cell Biology and Physiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63310; Growth Control and Cancer Group, National Institute of Environmental Health Science, Research Triangle Park, NC 27709; and School of Biomedical Science, University of Ulster, Coleraine BT521SA, Northern Ireland"}]},{"given":"C. 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