{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T01:24:23Z","timestamp":1773969863661,"version":"3.50.1"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,5,24]]},"abstract":"<jats:p>Strict regulation of DNA replication is essential to ensure proper duplication and segregation of chromosomes during the cell cycle, as its deregulation can lead to genomic instability and cancer. Thus, eukaryotic organisms have evolved multiple mechanisms to restrict DNA replication to once per cell cycle. Here, we show that inactivation of Geminin, an inhibitor of origin licensing, leads to rereplication in human normal and tumor cells within the same cell cycle. We found a CHK1-dependent checkpoint to be activated in rereplicating cells accompanied by formation of \u03b3H2AX and RAD51 nuclear foci. Abrogation of the checkpoint leads to abortive mitosis and death of rereplicated cells. In addition, we demonstrate that the induction of rereplication is dependent on the replication initiation factors CDT1 and CDC6, and independent of the functional status of p53. These data show that Geminin is required for maintaining genomic stability in human cells.<\/jats:p>","DOI":"10.1083\/jcb.200403106","type":"journal-article","created":{"date-parts":[[2004,5,24]],"date-time":"2004-05-24T22:34:17Z","timestamp":1085438057000},"page":"473-482","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":201,"title":["Loss of Geminin induces rereplication in the presence of functional p53"],"prefix":"10.1083","volume":"165","author":[{"given":"Marina","family":"Melixetian","sequence":"first","affiliation":[{"name":"1Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy"}]},{"given":"Andrea","family":"Ballabeni","sequence":"additional","affiliation":[{"name":"1Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy"}]},{"given":"Laura","family":"Masiero","sequence":"additional","affiliation":[{"name":"1Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy"}]},{"given":"Patrizia","family":"Gasparini","sequence":"additional","affiliation":[{"name":"2FIRC Institute of Molecular Oncology, 20122 Milan, Italy"}]},{"given":"Raffaella","family":"Zamponi","sequence":"additional","affiliation":[{"name":"1Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy"}]},{"given":"Jiri","family":"Bartek","sequence":"additional","affiliation":[{"name":"3Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark"}]},{"given":"Jiri","family":"Lukas","sequence":"additional","affiliation":[{"name":"3Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark"}]},{"given":"Kristian","family":"Helin","sequence":"additional","affiliation":[{"name":"1Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy"},{"name":"2FIRC Institute of Molecular Oncology, 20122 Milan, Italy"},{"name":"4Biotech Research and Innovation Center, DK-2100 Copenhagen, Denmark"}]}],"member":"291","published-online":{"date-parts":[[2004,5,24]]},"reference":[{"key":"2023072905252170500_BIB1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1126\/science.287.5460.2023","volume":"287","year":"2000","journal-title":"Science."},{"key":"2023072905252170500_BIB2","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/sj.onc.1205175","volume":"21","year":"2002","journal-title":"Oncogene."},{"key":"2023072905252170500_BIB3","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S1097-2765(03)00355-1","volume":"12","year":"2003","journal-title":"Mol. 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