Bent out of shape
Bent out of shape
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弯曲变形
DOI：
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Stéphane Larochelle
中科院分区：
文献类型：
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作者：
Stéphane Larochelle
在减数分裂期间，同源染色体必须重新组合以建立其适当分离所需的物理连接。重组是通过切除双链断裂（DSB）末端来产生与Rad51和Dmc1重组酶相关的单链DNA尾部来启动的。由此产生的核蛋白丝催化双链DNA入侵和链交换，连接同源对形成联合分子（JMs）。虽然Rad51和减数分裂特异性Dmc1共定位于核中心，并且两者都能促进体外链交换，但它们在减数分裂重组中是否具有同等作用尚不清楚。现在，Bishop和他的同事们创造了一种Rad51突变，这种突变使JM形成过程中的丝组装不偶联，从而剖析了酵母减数分裂过程中每种重组酶的功能贡献。他们发现，在减数分裂过程中，特异性地去除Rad51的jm形成活性对同源物之间的重组没有影响，而Dmc1的类似突变会产生严重的重组缺陷。然而，rad51jm活性对于有丝分裂DNA修复至关重要。虽然Dmc1形成的JM足以指导减数分裂期间正常的同源间重组，但这种活性是由Rad51调节的。作者表明，Rad51与已知的Dmc1辅助因子复合物Mei5-Sae3一起在体外刺激重组中间体的形成，Rad51 JM活性对于这种刺激是必不可少的。因此，Rad51通过刺激Dmc1活性间接参与减数分裂重组，通过催化链交换直接参与有丝分裂重组。（Science, 337, 1222-1225, 2012） BM分支调控
During meiosis, homologous chromosomes must recombine to establish the physical connections required for their proper segregation. Recombination is initiated by resection of double-strand break (DSB) ends to generate single-stranded DNA tails that associate with the Rad51 and Dmc1 recombinases. The resultant nucleoprotein filaments catalyze double-stranded DNA invasion and strand exchange that links homologous pairs to form joint molecules (JMs). Although Rad51 and meiosis-specific Dmc1 co-localize to nuclear foci, and both can promote strand exchange in vitro, it is not clear that they have equivalent roles in meiotic recombination. Now, Bishop and colleagues have created a Rad51 mutation that uncouples filament assembly from JM formation to dissect the functional contributions of each recombinase during meiosis in yeast. They show that specifically abolishing the JM-forming activity of Rad51 has no effect on recombination between homologs during meiosis, whereas the analogous mutation in Dmc1 produces severe recombination defects. However, Rad51 JM activity is essential for mitotic DNA repair. Although JM formation by Dmc1 is sufficient to direct normal interhomolog recombination during meiosis, this activity is regulated by Rad51. The authors show that Rad51 functions with the known Dmc1 cofactor complex Mei5–Sae3 to stimulate formation of recombination intermediates in vitro and that Rad51 JM activity is dispensable for this stimulation. Thus, Rad51 functions indirectly in meiotic recombination by stimulating Dmc1 activity and functions directly in mitotic recombination by catalyzing strand exchange. (Science 337, 1222–1225, 2012) BM branching regulation