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

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.

Meiosis in budding yeast

“…in spo11 ) does not trigger meiotic arrest, and indeed bypasses arrest in recombination defective mutants ( McKee and Kleckner 1997a ). Compared to the DDR, the substrate spectrum of Mec1 and Tel1 in the recombination checkpoint is greatly expanded to include numerous meiosis-specific proteins, presumably to help coordinate the progression of DSB repair with other meiotic processes ( Kar et al 2022 ). Recombination surveillance likely involves meiotic axis proteins, which, by a poorly understood mechanism dampen the activation of the canonical DDR effector kinase Rad53 and instead help activate the meiotic Rad53 paralogue Mek1 , via the phosphorylation of HORMA domain protein Hop1 , with possible involvement of a cytoplasmic component ( Lydall et al 1996 ; Carballo et al 2008 ; Cartagena-Lirola et al 2008 ; Herruzo et al 2021 ).…”