Neale_2020-03-03741A_FINAL_TEXTonlyB_AA_OpenAcess.pdf (59.32 MB)
Concerted cutting by Spo11 illuminates meiotic DNA break mechanics
journal contribution
posted on 2023-06-10, 01:21 authored by Dominic Johnson, Margaret Crawford, Timothy Cooper, Corentin Claeys Bouuaert, Scott Keeney, Bertrand Llorente, Valerie Garcia, Matt NealeMatt NealeGenetic recombination arises during meiosis through the repair of DNA double-strand breaks (DSBs) that are created by Spo11, a topoisomerase-like protein1,2. Spo11 DSBs form preferentially in nucleosome-depleted regions termed hotspots3,4, yet how Spo11 engages with its DNA substrate to catalyse DNA cleavage is poorly understood. Although most recombination events are initiated by a single Spo11 cut, here we show in Saccharomyces cerevisiae that hyperlocalized, concerted Spo11 DSBs separated by 33 to more than 100 base pairs also form, which we term ‘double cuts’. Notably, the lengths of double cuts vary with a periodicity of 10.5 base pairs, which is conserved in yeast and mice. This finding suggests a model in which the orientation of adjacent Spo11 molecules is fixed relative to the DNA helix—a proposal supported by the in vitro DNA-binding properties of the Spo11 core complex. Deep sequencing of meiotic progeny identifies recombination scars that are consistent with repair initiated from gaps generated by adjacent Spo11 DSBs. Collectively, these results revise our present understanding of the mechanics of Spo11-DSB formation and expand on the original concepts of gap repair during meiosis to include DNA gaps that are generated by Spo11 itself.
Funding
Spatial regulation of meiotic recombination; G2004; WELLCOME TRUST; 200843/Z/16/Z
Biochemical reconstitution of DNA repair reactions on intact chromatin; G0986; EUROPEAN UNION
History
Publication status
- Published
File Version
- Accepted version
Journal
NatureISSN
0028-0836Publisher
Nature ResearchExternal DOI
Volume
594Page range
572-576Event location
EnglandDepartment affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-10-11First Open Access (FOA) Date
2021-12-10First Compliant Deposit (FCD) Date
2021-10-08Usage metrics
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