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In this report, we highlight a new and interesting aspect of Cdt1 deregulation: data from several different systems all strongly indicate that unregulated Cdt1 overexpression at pathophysiological levels can induce chromosomal damage other than rereplication in non-transformed cells. The most important finding in these studies is that deregulated Cdt1 induces chromosomal damage and activation of the ATM-Chk2 DNA damage checkpoint pathway even in quiescent cells. These Cdt1 activities are negatively regulated by cyclin A\/Cdks, probably through modification by phosphorylation. Furthermore, we found that deregulated Cdt1 induces chromosomal instability in normal human cells. Since Cdt1 is overexpressed in cancer cells, this would be a new molecular mechanism leading to carcinogenesis.<\/jats:p>","DOI":"10.1242\/jcs.03031","type":"journal-article","created":{"date-parts":[[2006,7,12]],"date-time":"2006-07-12T03:23:30Z","timestamp":1152674610000},"page":"3128-3140","source":"Crossref","is-referenced-by-count":95,"title":["Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability"],"prefix":"10.1242","volume":"119","author":[{"given":"Yasutoshi","family":"Tatsumi","sequence":"first","affiliation":[{"name":"Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yugawa","sequence":"additional","affiliation":[{"name":"Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Narisawa-Saito","sequence":"additional","affiliation":[{"name":"Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Kiyono","sequence":"additional","affiliation":[{"name":"Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042519312148600_REF1","doi-asserted-by":"crossref","unstructured":"Arentson, E., Faloon, P., Seo, J., Moon, E., Studts, J. 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