Distinct and interdependent functions of three RING proteins regulate recombination during mammalian meiosis. Ito et al.

During meiosis, each pair of homologous chromosomes becomes connected by at least one crossover, as required for accurate segregation, and adjacent crossovers are widely separated thereby limiting total numbers. In coarsening models, this crossover patterning results from nascent recombination sites competing to accrue a limiting pro-crossover RING-domain protein (COR) that diffuses between synapsed chromosomes. Here we delineate the localization dynamics of three mammalian CORs in mouse and determine their interdependencies. RNF212, HEI10 and a new member RNF212B show divergent spatiotemporal dynamics along synapsed chromosomes, including profound differences in spermatocytes and oocytes, that are not easily reconciled by elementary coarsening models. Contrasting mutant phenotypes and genetic requirements indicate that RNF212B, RNF212, and HEI10 play distinct but interdependent functions in regulating meiotic recombination and coordinating the events of meiotic prophase-I by integrating signals from DNA breaks, homolog synapsis, the cell-cycle, and incipient crossover sites.

在减数分裂过程中，每对同源染色体通过至少一次交叉连接，这是确保准确分离的必要条件，且相邻交叉点广泛分布，从而限制了总交叉次数。在粗化模型中，这种交叉模式源于新兴重组位点的竞争，以积累限制性促交叉RING结构域蛋白（COR），该蛋白在配对的染色体之间扩散。在本研究中，我们描绘了三种哺乳动物COR在鼠中的定位动力学，并确定了它们之间的相互依赖关系。RNF212、HEI10以及一种新的成员RNF212B显示出在配对染色体上的时空动态差异，包括在精原细胞和卵母细胞中的显著差异，这些差异难以通过基本的粗化模型得到调和。对比突变表型和遗传需求表明，RNF212B、RNF212和HEI10在调节减数分裂和通过整合DNA断裂、同源配对、细胞周期和早期交叉位点信号来协调减数分裂前期I的事件中，发挥着不同但相互依赖的功能。