CONSERVATION OF THE CHK1 CHECKPOINT PATHWAY IN MAMMALS - LINKAGE OF DNA-DAMAGE TO CDK REGULATION THROUGH CDC25

Citation
Y. Sanchez et al., CONSERVATION OF THE CHK1 CHECKPOINT PATHWAY IN MAMMALS - LINKAGE OF DNA-DAMAGE TO CDK REGULATION THROUGH CDC25, Science, 277(5331), 1997, pp. 1497-1501
Citations number
26
Categorie Soggetti
Multidisciplinary Sciences
Journal title
ISSN journal
00368075
Volume
277
Issue
5331
Year of publication
1997
Pages
1497 - 1501
Database
ISI
SICI code
0036-8075(1997)277:5331<1497:COTCCP>2.0.ZU;2-H
Abstract
In response to DNA damage, mammalian cells prevent cell cycle progress ion through the control of critical cell cycle regulators. A human gen e was identified that encodes the protein Chk1, a homolog of the Schiz osaccharomyces pombe Chk1 protein kinase, which is required for the DN A damage checkpoint. Human Chk1 protein was modified in response to DN A damage. In vitro Chk1 bound to and phosphorylated the dual-specifici ty protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control cell cycle transitions by dephosphorylating cyclin-dependent kinases. Chk1 phosphorylates Cdc25C on serine-216. As shown in an accompanying pape r by Peng et al. in this issue, serine-216 phosphorylation creates a b inding site for 14-3-3 protein and inhibits function of the phosphatas e. These results suggest a model whereby in response to DNA damage, Ch k1 phosphorylates and inhibits Cdc25C, thus preventing activation of t he Cdc2-cyclin B complex and mitotic entry.