Laboratory of Development of the Gonads, UMR E008 Genetic Stability Stem Cells and Radiations, Université de Paris, Université Paris Saclay, CEA, F-92265, Fontenay aux Roses, France.
Laboratoire de Microscopie Moléculaire et Cellulaire, UMR 8126, Interactions Moléculaires et Cancer, CNRS, Université Paris Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.
DNA Repair (Amst). 2021 Jun;102:103097. doi: 10.1016/j.dnarep.2021.103097. Epub 2021 Mar 13.
During meiosis, programmed double-strand breaks are repaired by homologous recombination (HR) to form crossovers that are essential to homologous chromosome segregation. Single-stranded DNA (ssDNA) containing intermediates are key features of HR, which must be highly regulated. RPA, the ubiquitous ssDNA binding complex, was thought to play similar roles during mitotic and meiotic HR until the recent discovery of MEIOB and its partner, SPATA22, two essential meiosis-specific proteins. Here, we show that like MEIOB, SPATA22 resembles RPA subunits and binds ssDNA. We studied the physical and functional interactions existing between MEIOB, SPATA22, and RPA, and show that MEIOB and SPATA22 interact with the preformed RPA complex through their interacting domain and condense RPA-coated ssDNA in vitro. In meiotic cells, we show that MEIOB and SPATA22 modify the immunodetection of the two large subunits of RPA. Given these results, we propose that MEIOB-SPATA22 and RPA form a functional ssDNA-interacting complex to satisfy meiotic HR requirements by providing specific properties to the ssDNA.
在减数分裂过程中，通过同源重组（HR）修复有丝分裂的双链断裂，形成对同源染色体分离至关重要的交叉。含有中间产物的单链 DNA（ssDNA）是 HR 的关键特征，必须高度调控。普遍存在的 ssDNA 结合复合物 RPA 被认为在有丝分裂和减数分裂 HR 中发挥相似的作用，直到最近发现 MEIOB 及其伴侣 SPATA22，这两种必需的减数分裂特异性蛋白。在这里，我们表明，像 MEIOB 一样，SPATA22 类似于 RPA 亚基并结合 ssDNA。我们研究了 MEIOB、SPATA22 和 RPA 之间存在的物理和功能相互作用，并表明 MEIOB 和 SPATA22 通过其相互作用域与预先形成的 RPA 复合物相互作用，并在体外浓缩 RPA 包被的 ssDNA。在减数分裂细胞中，我们表明 MEIOB 和 SPATA22 修饰了 RPA 的两个大亚基的免疫检测。鉴于这些结果，我们提出 MEIOB-SPATA22 和 RPA 形成一个功能性的 ssDNA 相互作用复合物，通过为 ssDNA 提供特定的性质来满足减数分裂 HR 的要求。
