biostudies-literatureLopez Ruiz LMHuman Frontier Science ProgramEuropean Research CouncilNIDA NIH HHSWellcome TrustBiotechnology and Biological Sciences Research Councile1011140https://www.ebi.ac.uk/biostudies/studies/S-EPMC10936813biostudies-literatureUnknown20(3)During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we provide evidence that DPLoS geneticsMeiotic prophase length modulates Tel1-dependent DNA double-strand break interference.PMC10936813225852/Z/22/ZK05 DA000060311336BB/V005081/1BB/M010279/1CDA00060/2010200843/Z/16/ZLopez Ruiz LMBrown GGBJohnson DAllison RMNeale MJGittens WHfalseMeiotic prophase length modulates Tel1-dependent DNA double-strand break interference.During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we provide evidence that D2024-01-01T00:00:00Z2024 Mar2026-07-14T20:58:05.435Z2026-06-24T03:07:15.283ZS-EPMC109368133842768810.1371/journal.pgen.1011140