Reference - PMID:12023299 - Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III.
Reference summary
- PubMed ID
- PMID:12023299
- Title
- Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III.
- Authors
- Caspari T, Murray JM, Carr AM
- Citation
- Genes Dev 2002 May 15;16(10):1195-208
- Publication year
- 2002
- Abstract
- The availability of a sister chromatid, and thus the cell cycle phase in which DNA double-strand breaks (DSBs) occur, influences the choice between homologous recombination (HR) or nonhomologous end joining (NHEJ). The sequential activation and destruction of CDK-cyclin activities controls progression through the cell cycle. Here we provide evidence that the major Schizosaccharomyces pombe CDK, Cdc2-cyclin B, influences recombinational repair of radiation-induced DSBs during the G(2) phase at two distinct stages. At an early stage in HR, a defect in Cdc2 kinase activity, which is caused by a single amino acid change in cyclin B, affects the formation of Rhp51 (Rad51(sp)) foci in response to ionizing radiation in a process that is redundant with the function of Rad50. At a late stage in HR, low Cdc2-cyclin B activity prevents the proper regulation of topoisomerase III (Top3) function, disrupting a recombination step that occurs after the assembly of Rhp51 foci. This effect of Cdc2-cyclin B kinase on Top3 function is mediated by the BRCT-domain-containing checkpoint protein Crb2, thus linking checkpoint proteins directly with recombinational repair in G(2). Our data suggest a model in which CDK activity links processing of recombination intermediates to cell cycle progression via checkpoint proteins.
