Robert Thomas, Vrielynck Nathalie, Mézard Christine, de Massy Bernard, Grelon Mathilde
Institute of Human Genetics, UPR1142CNRS, Université de Montpellier, 141 Rue de la Cardonille, 34396 Montpellier Cedex 05, France.
Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, Université Paris-Saclay, RD10, 78026 Versailles Cedex, France.
Semin Cell Dev Biol. 2016 Jun;54:165-76. doi: 10.1016/j.semcdb.2016.02.025. Epub 2016 Mar 16.
Meiotic recombination is initiated by the formation of programmed DNA double-strand breaks (DSBs). More than 15 years ago, Spo11 was identified as the protein responsible for meiotic DSB formation, notably because of its striking similarities with the A subunit of topoisomerase VI (TopoVI). TopoVI are enzymes that modify DNA topology by generating transient DSBs and are active as heterotetramers, composed of two A and two B subunits. A2 dimers catalyse the DNA cleavage reaction, whereas the B subunits regulate A2 conformation, DNA capture, cleavage and re-ligation. The recent identification in plants and mammals of a B-like TopoVI subunit that interacts with SPO11 and is required for meiotic DSB formation makes us to reconsider our understanding of the meiotic DSB catalytic complex. We provide here an overview of the knowledge on TopoVI structure and mode of action and we compare them with their meiotic counterparts. This allows us to discuss the nature, structure and functions of the meiotic TopoVI-like complex during meiotic DSB formation.
减数分裂重组由程序性DNA双链断裂(DSB)的形成引发。15年多前,Spo11被鉴定为负责减数分裂DSB形成的蛋白质,特别是因为它与拓扑异构酶VI(TopoVI)的A亚基有显著相似性。TopoVI是通过产生瞬时DSB来改变DNA拓扑结构的酶,作为由两个A亚基和两个B亚基组成的异源四聚体发挥作用。A2二聚体催化DNA切割反应,而B亚基调节A2构象、DNA捕获、切割和重新连接。最近在植物和哺乳动物中鉴定出一种与SPO11相互作用且是减数分裂DSB形成所必需的类TopoVI B亚基,这使我们重新思考对减数分裂DSB催化复合物的理解。我们在此概述了关于TopoVI结构和作用模式的知识,并将它们与其减数分裂对应物进行比较。这使我们能够讨论减数分裂类TopoVI复合物在减数分裂DSB形成过程中的性质、结构和功能。