Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis.
Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis.
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DOI：
10.1016/j.cell.2011.08.032
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发表时间：
2011-09-30
期刊：
影响因子：
64.5
通讯作者：
West SC
中科院分区：
文献类型：
--
作者：
Matos J;Blanco MG;Maslen S;Skehel JM;West SC
DNA重组中间产物的有效和及时的拆分是双极染色体分离的关键。在这里，我们证明了减数分裂和有丝分裂的特殊染色体分离模式，需要重组与细胞周期进展的协调，是通过调节两个促进交叉的核酸内切酶的激活时间来实现的。在酵母减数分裂中，MUS81-MMS4和Yen1受导致其顺序激活的磷酸化事件的控制。MUS81-MMS4在减数分裂I中被Cdc5介导的磷酸化过度激活，产生染色体分离所需的交叉。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，一个类似的调控网络抑制这些核酸酶的活性，直到有丝分裂，使重组的结果偏向非交叉产物，同时也确保消除任何持久的联合分子。有丝分裂调控因此有助于染色体分离，同时限制杂合性丧失和姐妹染色单体交换的可能性。
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 non-crossover 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.
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