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

Caspari, Thomas, Murray, Johanne M and Carr, Antony M (2002) Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III. Genes and Development, 16 (10). pp. 1195-208. ISSN 0890-9369

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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.

Item Type: Article
Additional Information: JM 40% contribution, designed and helped execute the experiments relating to rqh1 and Top3 (Figs 4,5 and 6) . All Sussex authors. First demonstration of a role for crb2 in repair and rqh1/top3 in the resolution of recombination.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Johanne Murray
Date Deposited: 06 Feb 2012 19:25
Last Modified: 13 Nov 2012 14:56
URI: http://sro.sussex.ac.uk/id/eprint/20472
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