Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability

Yasutoshi Tatsumi, Nozomi Sugimoto, Takashi Yugawa, Mako Narisawa-Saito, Tohru Kiyono, Masatoshi Fujita

研究成果: Contribution to journalArticle査読

87 被引用数 (Scopus)


The activity of human Cdtl is negatively regulated by multiple mechanisms. This suggests that Cdtl deregulation may have a deleterious effect. Indeed, it has been suggested that overexpression of Cdt1 can induce rereplication in cancer cells and that rereplication activates Ata3da-telangiectasia-mutated (ATM) kinase and/or ATM- and Rad3-related (ATR) kinase-dependent checkpoint pathways. In this report, we highlight a new and interesting aspect of Cdt1 deregulation: data from several different systems all strongly indicate that unregulated Cdtl 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 Cdtl 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 Cdtl induces chromosomal instability in normal human cells. Since Cdt1 is overexpressed in cancer cells, this would be a new molecular mechanism leading to carcinogenesis.

ジャーナルJournal of cell science
出版ステータス出版済み - 8 1 2006

All Science Journal Classification (ASJC) codes

  • 細胞生物学


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