CDK contribution to DSB formation and recombination in fission yeast meiosis

PLoS Genet. 2019 Jan 14;15(1):e1007876. doi: 10.1371/journal.pgen.1007876. eCollection 2019 Jan.

Abstract

CDKs (cyclin-dependent kinases) associate with different cyclins to form different CDK-complexes that are fundamental for an ordered cell cycle progression, and the coordination of this progression with different aspects of the cellular physiology. During meiosis programmed DNA double-strand breaks (DSBs) initiate recombination that in addition to generating genetic variability are essential for the reductional chromosome segregation during the first meiotic division, and therefore for genome stability and viability of the gametes. However, how meiotic progression and DSB formation are coordinated, and the role CDKs have in the process, is not well understood. We have used single and double cyclin deletion mutants, and chemical inhibition of global CDK activity using the cdc2-asM17 allele, to address the requirement of CDK activity for DSB formation and recombination in fission yeast. We report that several cyclins (Cig1, Cig2, and the meiosis-specific Crs1) control DSB formation and recombination, with a major contribution of Crs1. Moreover, complementation analysis indicates specificity at least for this cyclin, suggesting that different CDK complexes might act in different pathways to promote recombination. Down-regulation of CDK activity impinges on the formation of linear elements (LinEs, protein complexes required for break formation at most DSB hotspot sites). This defect correlates with a reduction in the capability of one structural component (Rec25) to bind chromatin, suggesting a molecular mechanism by which CDK controls break formation. However, reduction in DSB formation in cyclin deletion mutants does not always correspondingly correlate with a proportional reduction in meiotic recombination (crossovers), suggesting that specific CDK complexes might also control downstream events balancing repair pathways. Therefore, our work points to CDK regulation of DSB formation as a key conserved feature in the initiation of meiotic recombination, in addition to provide a view of possible roles CDK might have in other steps of the recombination process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin B / genetics*
  • Cyclin-Dependent Kinases / genetics
  • Cyclins / genetics*
  • DNA Breaks, Double-Stranded
  • Genome, Fungal / genetics
  • Genomic Instability / genetics
  • Meiosis / genetics*
  • Multiprotein Complexes / genetics
  • Nuclear Proteins
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces pombe Proteins / genetics*

Substances

  • Cig1 protein, S pombe
  • Cig2 protein, S pombe
  • Crs1 protein, S pombe
  • Cyclin B
  • Cyclins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Rec25 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Cyclin-Dependent Kinases

Grants and funding

This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) FEDER-BFU2013-45182-P to MS and CMC, and MEIONet BFU2015-71786-REDT to CMC, and from Junta de Castilla y León (CSI084U16) to CMC. IBFG is funded by Junta de Castilla y León, Program "Escalera de Excelencia" FEDER-CLU-2017-03. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.