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- W4328129462 abstract "ABSTRACT 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 demonstrate that DSB clustering is abolished when meiotic prophase timing is extended via deletion of the NDT80 transcription factor. We propose that extension of meiotic prophase enables most cells, and therefore most chromosomal domains within them, to reach an equilibrium state of similar Spo11-DSB potential, reducing the impact that priming has on estimates of coincident DSB formation. Consistent with this view, genome-wide maps of Spo11-DSB formation generated in the absence of Tel1 are skewed towards regions that load pro-DSB factors early—revealing regions of preferential priming—but this effect is abolished when NDT80 is deleted. Our work highlights how the stochastic nature of Spo11-DSB formation in individual cells within the limited temporal window of meiotic prophase can cause localised DSB clustering—a phenomenon that is exacerbated in tel1 Δ cells due to the dual roles that Tel1 has in DSB interference and meiotic prophase checkpoint control." @default.
- W4328129462 created "2023-03-22" @default.
- W4328129462 creator A5001405263 @default.
- W4328129462 creator A5006862779 @default.
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- W4328129462 creator A5037211178 @default.
- W4328129462 creator A5063601016 @default.
- W4328129462 creator A5074609609 @default.
- W4328129462 date "2023-03-20" @default.
- W4328129462 modified "2023-10-16" @default.
- W4328129462 title "Meiotic prophase length modulates Tel1-dependent DNA double-strand break interference" @default.
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