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

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3128-3140
Number of pages13
JournalJournal of Cell Science
Volume119
Issue number15
DOIs
Publication statusPublished - Aug 1 2006
Externally publishedYes

Fingerprint

Chromosomal Instability
Telangiectasis
Phosphotransferases
Cyclin A
Human Activities
DNA Damage
Neoplasms
Carcinogenesis
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability. / Tatsumi, Yasutoshi; Sugimoto, Nozomi; Yugawa, Takashi; Narisawa-Saito, Mako; Kiyono, Tohru; Fujita, Masatoshi.

In: Journal of Cell Science, Vol. 119, No. 15, 01.08.2006, p. 3128-3140.

Research output: Contribution to journalArticle

Tatsumi, Yasutoshi ; Sugimoto, Nozomi ; Yugawa, Takashi ; Narisawa-Saito, Mako ; Kiyono, Tohru ; Fujita, Masatoshi. / Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability. In: Journal of Cell Science. 2006 ; Vol. 119, No. 15. pp. 3128-3140.
@article{c99cb9b0024f44d7b0e9611a99ef3e70,
title = "Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability",
abstract = "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.",
author = "Yasutoshi Tatsumi and Nozomi Sugimoto and Takashi Yugawa and Mako Narisawa-Saito and Tohru Kiyono and Masatoshi Fujita",
year = "2006",
month = "8",
day = "1",
doi = "10.1242/jcs.03031",
language = "English",
volume = "119",
pages = "3128--3140",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "15",

}

TY - JOUR

T1 - Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability

AU - Tatsumi, Yasutoshi

AU - Sugimoto, Nozomi

AU - Yugawa, Takashi

AU - Narisawa-Saito, Mako

AU - Kiyono, Tohru

AU - Fujita, Masatoshi

PY - 2006/8/1

Y1 - 2006/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33748305620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748305620&partnerID=8YFLogxK

U2 - 10.1242/jcs.03031

DO - 10.1242/jcs.03031

M3 - Article

VL - 119

SP - 3128

EP - 3140

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 15

ER -