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

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The meiotic DNA break response is shown to involve a large number of phosphorylation changes and a clearly detectable transcriptional response. By contrast, the meiotic proteome remains remarkably unchanged in… Click to show full abstract

The meiotic DNA break response is shown to involve a large number of phosphorylation changes and a clearly detectable transcriptional response. By contrast, the meiotic proteome remains remarkably unchanged in response to breaks. 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.

Keywords: dna; meiotic dna; dna breaks; dna break; response

Journal Title: Life Science Alliance
Year Published: 2022

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