A novel function for CDK2 activity at meiotic crossover sites

Research output: Contribution to journalArticle

Abstract

Genetic diversity in offspring is induced by meiotic recombination, which is initiated between homologs at >200 sites originating from meiotic double-strand breaks (DSBs). Of this initial pool, only 1-2 DSBs per homolog pair will be designated to form meiotic crossovers (COs), where reciprocal genetic exchange occurs between parental chromosomes. Cyclin-dependent kinase 2 (CDK2) is known to localize to so-called "late recombination nodules" (LRNs) marking incipient CO sites. However, the role of CDK2 kinase activity in the process of CO formation remains uncertain. Here, we describe the phenotype of 2 Cdk2 point mutants with elevated or decreased activity, respectively. Elevated CDK2 activity was associated with increased numbers of LRN-associated proteins, including CDK2 itself and the MutL homolog 1 (MLH1) component of the MutLγ complex, but did not lead to increased numbers of COs. In contrast, reduced CDK2 activity leads to the complete absence of CO formation during meiotic prophase I. Our data suggest an important role for CDK2 in regulating MLH1 focus numbers and that the activity of this kinase is a key regulatory factor in the formation of meiotic COs.

Details

Authors
  • Nathan Palmer
  • S Zakiah A Talib
  • Priti Singh
  • Christine M F Goh
  • Kui Liu
  • John C Schimenti
  • Philipp Kaldis
Organisations
External organisations
  • A*Star Institute of Molecular and Cell Biology (IMCB)
  • Cornell University
  • University of Hong Kong
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Article numbere3000903
JournalPLoS Biology
Volume18
Issue number10
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes