London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
Cell. 2011 Sep 30;147(1):158-72. doi: 10.1016/j.cell.2011.08.032.
The efficient and timely resolution of DNA recombination intermediates is essential for bipolar chromosome segregation. Here, we show that the specialized chromosome segregation patterns of meiosis and mitosis, which require the coordination of recombination with cell-cycle progression, are achieved by regulating the timing of activation of two crossover-promoting endonucleases. In yeast meiosis, Mus81-Mms4 and Yen1 are controlled by phosphorylation events that lead to their sequential activation. Mus81-Mms4 is hyperactivated by Cdc5-mediated phosphorylation in meiosis I, generating the crossovers necessary for chromosome segregation. Yen1 is also tightly regulated and is activated in meiosis II to resolve persistent Holliday junctions. In yeast and human mitotic cells, a similar regulatory network restrains these nuclease activities until mitosis, biasing the outcome of recombination toward noncrossover products while also ensuring the elimination of any persistent joint molecules. Mitotic regulation thereby facilitates chromosome segregation while limiting the potential for loss of heterozygosity and sister-chromatid exchanges.
DNA 重组中间体的有效和及时解决对于双极染色体分离至关重要。在这里，我们表明，减数分裂和有丝分裂中特殊的染色体分离模式需要将重组与细胞周期进程协调起来，这是通过调节两种促进交叉的内切酶的激活时间来实现的。在酵母减数分裂中，Mus81-Mms4 和 Yen1 受到磷酸化事件的控制，这些事件导致它们的顺序激活。Mus81-Mms4 在减数分裂 I 中被 Cdc5 介导的磷酸化高度激活，产生了用于染色体分离的交叉。Yen1 也受到严格的调控，并在减数分裂 II 中被激活，以解决持续的 Holliday 连接。在酵母和人类有丝分裂细胞中，类似的调控网络抑制这些核酸酶的活性，直到有丝分裂，使重组的结果偏向于非交叉产物，同时也确保消除任何持续的联合分子。因此，有丝分裂调节促进了染色体分离，同时限制了杂合性丢失和姐妹染色单体交换的可能性。
