Dbf4-dependent CDC7 kinase links DNA replication to the segregation of homologous chromosomes in meiosis I

Cell. 2008 Nov 14;135(4):662-78. doi: 10.1016/j.cell.2008.10.026.

Abstract

Meiosis differs from mitosis in that DNA replication is followed by the segregation of homologous chromosomes but not sister chromatids. This depends on the formation of interhomolog connections through crossover recombination and on the attachment of sister kinetochores to microtubules emanating from the same spindle pole. We show that in yeast, the Dbf4-dependent Cdc7 kinase (DDK) provides a link between premeiotic S phase, recombination, and monopolar attachment. Independently from its established role in initiating DNA replication, DDK promotes double-strand break formation, the first step of recombination, and the recruitment of the monopolin complex to kinetochores, which is essential for monopolar attachment. DDK regulates monopolin localization together with the polo-kinase Cdc5 bound to Spo13, probably through phosphorylation of the monopolin subunit Lrs4. Thus, activation of DDK both initiates DNA replication and commits meiotic cells to reductional chromosome segregation in the first division of meiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology*
  • Chromosomes / ultrastructure
  • DNA Replication
  • Gene Deletion
  • Kinetochores / metabolism
  • Kinetochores / ultrastructure
  • Meiosis*
  • Microtubules / metabolism
  • Models, Biological
  • Models, Genetic
  • Nuclear Proteins / metabolism
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / physiology*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • Dbf4 protein, S cerevisiae
  • LRS4 protein, S cerevisiae
  • Nuclear Proteins
  • SPO13 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • CDC7 protein, S cerevisiae
  • CDC7 protein, human
  • Protein-Serine-Threonine Kinases
  • CDC5 protein, S cerevisiae