Cell cycle: Checkpoint Pathways

Abstract

The checkpoint mechanism by which budding yeast Saccharomyces cerevisiae achieve mitotic arrest in response to DNA damage has been studied by Sanchez et al . In mammalian cells and the fission yeast Saccharomyces pombe , DNA damage causes arrest through inhibitory tyrosine phosphorylation of cyclin-dependent kinase complexes, but such phosphorylation is not required in S. cerevisiae . Nevertheless, the authors show a role for a homolog of the Chk1 protein kinase that functions in checkpoint signaling in S. pombe and mammalian cells. Chk1 acts independently of the Rad53 protein kinase that also participates in the response to DNA damage: Whereas Chk1 apparently phoshorylates the anaphase inhibitor protein Pds1 and thus prevents its degradation, Rad53 appears to prevent exit from mitosis by inhibiting the activity of yet another kinase, Cdc5. The evidence indicates that Chk1 and Rad53 function in branches of the checkpoint pathway that primarily inhibit entry into anaphase and exit from mitosis, respectively, but that they can also support the maintenance of arrest through the alternate branch of the pathway as well. Sanchez, Y., Bachant, J., Wang, H., Hu, F., Liu, D., Tetzlaff, M., and Elledge, S.J. (1999) Control of the DNA damage checkpoint by Chk1 and Rad53 protein kinases through distinct mechanisms. Science 286 : 1166-1171. [Abstract] [Full Text]