Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III

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 progressi...

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Bibliographic Details
Published in:Genes & development 2002-05, Vol.16 (10), p.1195-1208
Main Authors: Caspari, Thomas, Murray, Johanne M, Carr, Antony M
Format: Article
Language:English
Subjects:
CDC2 Protein Kinase - metabolism
CDC28 Protein Kinase, S cerevisiae - metabolism
Cell Cycle Proteins - metabolism
Cell Division - physiology
Cell Division - radiation effects
Cell Extracts
Cells, Cultured - physiology
Cells, Cultured - radiation effects
Cyclin B - metabolism
DNA Helicases - metabolism
DNA Replication - physiology
DNA Topoisomerases, Type I - metabolism
Fungal Proteins - metabolism
Genes, cdc - physiology
Nuclear Proteins - metabolism
Point Mutation
Precipitin Tests
Recombination, Genetic
Research Paper
Schizosaccharomyces - genetics
Schizosaccharomyces - physiology
Schizosaccharomyces pombe Proteins
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.221402