Regulation of Cdc45 in the cell cycle and after DNA damage.
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.
Broderick
Ronan
R
Department of Biochemistry, National University of Ireland, Cell Cycle Control Group, Centre for Chromosome Biology, Galway, Galway, Ireland. ronan.broderick@gmail.com
Nasheuer
Heinz-Peter
HP
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological
C113571:CDC45 protein, human; D018797:Cell Cycle Proteins