Proline-rich protein PRR19 functions with cyclin-like CNTD1 to promote meiotic crossing over in mouse

Nat Commun. 2020 Jun 18;11(1):3101. doi: 10.1038/s41467-020-16885-3.

Abstract

Orderly chromosome segregation is enabled by crossovers between homologous chromosomes in the first meiotic division. Crossovers arise from recombination-mediated repair of programmed DNA double-strand breaks (DSBs). Multiple DSBs initiate recombination, and most are repaired without crossover formation, although one or more generate crossovers on each chromosome. Although the underlying mechanisms are ill-defined, the differentiation and maturation of crossover-specific recombination intermediates requires the cyclin-like CNTD1. Here, we identify PRR19 as a partner of CNTD1. We find that, like CNTD1, PRR19 is required for timely DSB repair and the formation of crossover-specific recombination complexes. PRR19 and CNTD1 co-localise at crossover sites, physically interact, and are interdependent for accumulation, indicating a PRR19-CNTD1 partnership in crossing over. Further, we show that CNTD1 interacts with a cyclin-dependent kinase, CDK2, which also accumulates in crossover-specific recombination complexes. Thus, the PRR19-CNTD1 complex may enable crossover differentiation by regulating CDK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomes / genetics
  • Crossing Over, Genetic / genetics*
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclins / genetics*
  • DNA Breaks, Double-Stranded*
  • DNA Damage / genetics
  • DNA Repair / genetics
  • Female
  • Homologous Recombination / genetics
  • Male
  • Meiosis / genetics*
  • Mice

Substances

  • CNTD1 protein, mouse
  • Cyclins
  • Cyclin-Dependent Kinase 2