Mol Cell 2000 Sep 01;63:649-59. doi: 10.1016/s1097-2765(00)00063-0.

Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage.

???displayArticle.abstract???
Cell cycle checkpoints lead to the inhibition of cell cycle progression following DNA damage. A cell-free system derived from Xenopus eggs has been established that reconstitutes the checkpoint pathway inhibiting DNA replication initiation. DNA containing double-strand breaks inhibits replication initiation in a dose-dependent manner. Upon checkpoint activation, a prereplicative complex is assembled that contains ORC, Cdc6, Cdc7, and MCM proteins but lacks Cdc45. The checkpoint is ATM dependent. Cdk2/CyclinE acts downstream of ATM and is downregulated by Cdk2 phosphorylation on tyrosine 15. Cdk2AF/CyclinE is refractory to checkpoint signaling, and Cdc25A overrides the checkpoint and restores DNA replication. This report provides the description of a DNA damage checkpoint pathway that prevents the onset of S phase independently of the transcriptional function of p53 in a vertebrate organism.

???displayArticle.pubmedLink??? 11030344
???displayArticle.link??? Mol Cell
???displayArticle.grants??? [+]

Species referenced: Xenopus
Genes referenced: atm cdc25a cdc45 cdc6 cdc7 cdk2 mmut tp53