Concerted cutting by Spo11 illuminates meiotic DNA break mechanics

Johnson, Dominic, Crawford, Margaret, Cooper, Tim, Claeys Bouuaert, Corentin, Keeney, Scott, Llorente, Bertrand, Garcia, Valerie and Neale, Matthew J (2021) Concerted cutting by Spo11 illuminates meiotic DNA break mechanics. Nature, 594. pp. 572-576. ISSN 0028-0836

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Genetic 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 11 Oct 2021 09:35
Last Modified: 28 Feb 2022 16:23

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Project NameSussex Project NumberFunderFunder Ref
Biochemical reconstitution of DNA repair reactions on intact chromatinG0986EUROPEAN UNIONUnset
Spatial regulation of meiotic recombinationG2004WELLCOME TRUST200843/Z/16/Z