Meiotic DNA breaks activate a streamlined phospho-signaling response that largely avoids protein-level changes

Life Sci Alliance. 2022 Sep 1;5(10):e202201454. doi: 10.26508/lsa.202201454. Print 2022 Oct.

Abstract

Meiotic cells introduce a numerous programmed DNA breaks into their genome to stimulate meiotic recombination and ensure controlled chromosome inheritance and fertility. A checkpoint network involving key kinases and phosphatases coordinates the repair of these DNA breaks, but the precise phosphorylation targets remain poorly understood. It is also unknown whether meiotic DNA breaks change gene expression akin to the canonical DNA-damage response. To address these questions, we analyzed the meiotic DNA break response in Saccharomyces cerevisiae using multiple systems-level approaches. We identified 332 DNA break-dependent phosphorylation sites, vastly expanding the number of known events during meiotic prophase. Less than half of these events occurred in recognition motifs for the known meiotic checkpoint kinases Mec1 (ATR), Tel1 (ATM), and Mek1 (CHK2), suggesting that additional kinases contribute to the meiotic DNA-break response. We detected a clear transcriptional program but detected only very few changes in protein levels. We attribute this dichotomy to a decrease in transcript levels after meiotic entry that dampens the effects of break-induced transcription sufficiently to cause only minimal changes in the meiotic proteome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • DNA Breaks, Double-Stranded
  • DNA-Binding Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Meiosis* / genetics
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Proteome / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Protein Serine-Threonine Kinases
  • Cell Cycle Proteins
  • Proteome
  • Intracellular Signaling Peptides and Proteins
  • DNA-Binding Proteins
  • Phosphoric Monoester Hydrolases
  • TEL1 protein, S cerevisiae