Temporospatial coordination of meiotic DNA replication and recombination via DDK recruitment to replisomes

Cell. 2014 Aug 14;158(4):861-873. doi: 10.1016/j.cell.2014.06.028.

Abstract

It has been long appreciated that, during meiosis, DNA replication is coordinated with the subsequent formation of the double-strand breaks (DSBs) that initiate recombination, but a mechanistic understanding of this process was elusive. We now show that, in yeast, the replisome-associated components Tof1 and Csm3 physically associate with the Dbf4-dependent Cdc7 kinase (DDK) and recruit it to the replisome, where it phosphorylates the DSB-promoting factor Mer2 in the wake of the replication fork, synchronizing replication with an early prerequisite for DSB formation. Recruiting regulatory kinases to replisomes may be a general mechanism to ensure spatial and temporal coordination of replication with other chromosomal processes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • DNA Breaks, Double-Stranded*
  • DNA Replication*
  • DNA-Binding Proteins / metabolism
  • Meiosis*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinases / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • CSM1 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Dbf4 protein, S cerevisiae
  • Nuclear Proteins
  • REC107 protein, S cerevisiae
  • REC114 protein, S cerevisiae
  • Recombinases
  • Saccharomyces cerevisiae Proteins
  • TOF1 protein, S cerevisiae
  • CDC7 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases

Associated data

  • GEO/GSE52970
  • GEO/GSE52987