Tel1(ATM)-mediated interference suppresses clustered meiotic double-strand-break formation

Garcia, Valerie, Gray, Stephen, Allison, Rachal M, Cooper, Tim J and Neale, Matthew J (2015) Tel1(ATM)-mediated interference suppresses clustered meiotic double-strand-break formation. Nature, 520. pp. 114-118. ISSN 1476-4687

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Meiotic recombination is a critical step in gametogenesis for many organisms, enabling the creation of genetically diverse haploid gametes. In each meiotic cell, recombination is initiated by numerous DNA double-strand breaks (DSBs) created by Spo11, the evolutionarily conserved topoisomerase-like protein, but how these DSBs are distributed relatively uniformly across the four chromatids that make up each chromosome pair is poorly understood. Here we employ Saccharomyces cerevisiae to demonstrate distance-dependent DSB interference in cis (in which the occurrence of a DSB suppresses adjacent DSB formation)-a process that is mediated by the conserved DNA damage response kinase, Tel1(ATM). The inhibitory function of Tel1 acts on a relatively local scale, while over large distances DSBs have a tendency to form independently of one another even in the presence of Tel1. Notably, over very short distances, loss of Tel1 activity causes DSBs to cluster within discrete zones of concerted DSB activity. Our observations support a hierarchical view of recombination initiation where Tel1(ATM) prevents clusters of DSBs, and further suppresses DSBs within the surrounding chromosomal region. Such collective negative regulation will help to ensure that recombination events are dispersed evenly and arranged optimally for genetic exchange and efficient chromosome segregation.

Item Type: Article
Keywords: Tel1, ATM, Meiosis, DSB, Interference
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > Q Science (General)
Depositing User: Tim Cooper
Date Deposited: 15 Jan 2015 11:48
Last Modified: 18 Nov 2020 08:35

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Project NameSussex Project NumberFunderFunder Ref
Biochemical reconstitution of DNA repair reactions on intact chromatinG0986EUROPEAN UNION311336
Processing of Spo11-induced covalent protein-linked DNA double-strand breaks in meiosisG0137MRC-MEDICAL RESEARCH COUNCILG0800005