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

Hajime Murakami1, Scott Keeney2

  • 1Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Cell
|August 16, 2014
PubMed

Insights

Researchers discovered how DNA replication coordinates with double-strand break (DSB) formation during meiosis. The study shows replisome components recruit a kinase to phosphorylate a DSB-promoting factor, synchronizing these crucial events.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Meiosis involves DNA replication coordinated with double-strand break (DSB) formation, initiating recombination.
  • The precise mechanistic link between replication and DSB formation has remained unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism coordinating DNA replication with DSB formation during meiosis.
  • To identify factors that link the replisome to DSB initiation machinery.

Main Methods:

  • Yeast genetics and molecular biology techniques were employed.
  • Co-immunoprecipitation assays were used to study protein interactions.
  • Phosphorylation events were analyzed in vivo.

Main Results:

  • Tof1 and Csm3, associated with the replisome, physically interact with Dbf4-dependent Cdc7 kinase (DDK).
  • Tof1 and Csm3 recruit DDK to the replisome.
  • DDK phosphorylates Mer2 in the wake of the replication fork, synchronizing replication with DSB formation.
  • This recruitment ensures spatial and temporal coordination of replication with DSB formation.

Conclusions:

  • The study reveals a novel mechanism where replisome-associated proteins recruit a kinase to coordinate DNA replication with DSB formation.
  • This coordination is essential for initiating meiotic recombination.
  • Recruiting regulatory kinases to replisomes may be a general strategy for coordinating DNA replication with other chromosomal processes.

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