Syracuse

Concerted cutting by Spo11 illuminates meiotic DNA break mechanics

Archive ouverte

Johnson, Dominic | Crawford, Margaret | Cooper, Tim | Claeys Bouuaert, Corentin | Keeney, Scott | Llorente, Bertrand | Garcia, Valerie | Neale, Matthew, J

Edité par CCSD ; Nature Publishing Group -

International audience. Genetic recombination arises during meiosis via repair of DNA double-strand breaks (DSBs) created by the topoisomerase-like Spo11 protein 1,2. Spo11 DSBs form preferentially in nucleosome-depleted regions termed hotspots 3,4 , yet how Spo11 engages with its DNA substrate to catalyse DNA cleavage is poorly understood. Whilst most recombination events are initiated by a singular Spo11 cut, we demonstrate that hyper-localised, concerted Spo11 DSBs-double-cuts-also form, separated by just ~33 to over 100 base pairs. Remarkably, double-cut lengths vary with a periodicity of ~10.5 base pairs, conserved in yeast and mouse, invoking a model where the orientation of adjacent Spo11 molecules is fixed relative to the DNA helix-a proposal supported by in vitro DNA-binding properties of the Spo11 core complex. Deep sequencing meiotic progeny identifies recombination scars consistent with repair initiated from gaps generated by adjacent Spo11 DSBs. Collectively, these results revise current thinking about the mechanics of Spo11-DSB formation and expand upon the original concepts of gap repair during meiosis to include DNA gaps generated by Spo11 itself.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion