Tel1ATM-mediated interference suppresses clustered meiotic double-strand-break formation

Garcia, Valerie; Gray, Stephen; Allison, Rachal M.; Cooper, Tim J.; Neale, Matthew J.

Abstract

©2015 Macmillan Publishers Limited. All rights reserved. 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, Tel1ATM. 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 Tel1ATM 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.

Citation

Garcia, V., Gray, S., Allison, R. M., Cooper, T. J., & Neale, M. J. (2015). Tel1ATM-mediated interference suppresses clustered meiotic double-strand-break formation. Nature, 520(7545), 114-118. https://doi.org/10.1038/nature13993

• Journal Article Type: Article
• Acceptance Date: Oct 27, 2014
• Online Publication Date: Jan 5, 2015
• Publication Date: 2015-04
• Deposit Date: Nov 11, 2019
• Journal: Nature
• Print ISSN: 0028-0836
• Electronic ISSN: 1476-4687
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 520
• Issue: 7545
• Pages: 114-118
• DOI: https://doi.org/10.1038/nature13993
• Public URL: https://nottingham-repository.worktribe.com/output/3198990
• Publisher URL: https://www.nature.com/articles/nature13993
• Additional Information: Received: 25 March 2014; Accepted: 27 October 2014; First Online: 5 January 2015; : The authors declare no competing financial interests.