Holloway J Kim, Sun Xianfei, Yokoo Rayka, Villeneuve Anne M, Cohen Paula E
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Department of Developmental Biology and Department of Genetics, Stanford University, Stanford, CA 94305 Department of Developmental Biology and Department of Genetics, Stanford University, Stanford, CA 94305.
J Cell Biol. 2014 Jun 9;205(5):633-41. doi: 10.1083/jcb.201401122. Epub 2014 Jun 2.
Meiotic crossovers (COs) are crucial for ensuring accurate homologous chromosome segregation during meiosis I. Because the double-strand breaks (DSBs) that initiate meiotic recombination greatly outnumber eventual COs, this process requires exquisite regulation to narrow down the pool of DSB intermediates that may form COs. In this paper, we identify a cyclin-related protein, CNTD1, as a critical mediator of this process. Disruption of Cntd1 results in failure to localize CO-specific factors MutLγ and HEI10 at designated CO sites and also leads to prolonged high levels of pre-CO intermediates marked by MutSγ and RNF212. These data show that maturation of COs is intimately coupled to deselection of excess pre-CO sites to yield a limited number of COs and that CNTD1 coordinates these processes by regulating the association between the RING finger proteins HEI10 and RNF212 and components of the CO machinery.
减数分裂交叉互换（COs）对于确保减数第一次分裂期间同源染色体的准确分离至关重要。由于启动减数分裂重组的双链断裂（DSBs）数量远多于最终的COs，因此该过程需要精确调控，以缩小可能形成COs的DSB中间体池。在本文中，我们鉴定出一种细胞周期蛋白相关蛋白CNTD1，它是这一过程的关键调节因子。Cntd1的破坏导致CO特异性因子MutLγ和HEI10无法定位在指定的CO位点，还导致以MutSγ和RNF212为标记的CO前体中间体水平长时间维持在高位。这些数据表明，COs的成熟与过量CO前体位点的淘汰密切相关，从而产生有限数量的COs，并且CNTD1通过调节RING指蛋白HEI10和RNF212与CO机制组件之间的关联来协调这些过程。
