Regulation of Cdc45 in the cell cycle and after DNA damage.

Abstract:

:The Cdc (cell division cycle) 45 protein has a central role in the regulation of the initiation and elongation stages of eukaryotic chromosomal DNA replication. In addition, it is the main target for a Chk1 (checkpoint kinase 1)-dependent Cdc25/CDK2 (cyclin-dependent kinase 2)-independent DNA damage checkpoint signal transduction pathway following low doses of BPDE (benzo[a]pyrene dihydrodiol epoxide) treatment, which causes DNA damage similar to UV-induced adducts. Cdc45 interacts physically and functionally with the putative eukaryotic replicative DNA helicase, the MCM (mini-chromosome maintenance) complex, and forms a helicase active 'supercomplex', the CMG [Cdc45-MCM2-7-GINS (go-ichi-ni-san)] complex. These known protein-protein interactions, as well as unknown interactions and post-translational modifications, may be important for the regulation of Cdc45 and the initiation of DNA replication following DNA damage. Future studies will help to elucidate the molecular basis of this newly identified S-phase checkpoint pathway which has Cdc45 as a target.

journal_name

Biochem Soc Trans

authors

Broderick R,Nasheuer HP

doi

10.1042/BST0370926

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

926-30

issue

Pt 4

eissn

0300-5127

issn

1470-8752

pii

BST0370926

journal_volume

37

pub_type

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