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

Genes Dev. 2002 May 15;16(10):1195-208. doi: 10.1101/gad.221402.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / physiology*
  • Schizosaccharomyces pombe Proteins*

Substances

  • Cell Cycle Proteins
  • Cell Extracts
  • Crb2 protein, S pombe
  • Cyclin B
  • Fungal Proteins
  • Nuclear Proteins
  • Schizosaccharomyces pombe Proteins
  • CDC2 Protein Kinase
  • CDC28 Protein Kinase, S cerevisiae
  • DNA Helicases
  • Rqh1 protein, S pombe
  • DNA Topoisomerases, Type I