Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions.
Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions.
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DOI：
10.1016/j.molcel.2010.11.032
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发表时间：
2010-12-22
期刊：
影响因子：
16
通讯作者：
Hunter N
中科院分区：
文献类型：
--
作者：
Zakharyevich K;Ma Y;Tang S;Hwang PY;Boiteux S;Hunter N
Rad2/XPG 家族核酸酶 Exo1 在多种 DNA 修复途径中发挥作用。在减数分裂过程中，Exo1 促进交换，从而促进第一次分裂时的染色体分离。减数分裂重组是由程序化的 DNA 双链断裂 (DSB) 启动的。 DSB 的溶核切除会产生长的 3'-单链尾部，该尾部与同源染色体进行链交换，形成联合分子 (JM) 中间体。我们表明，减数分裂 DSB 切除在 exo1Δ 突变体中显着减少，并测试了 Exo1 催化切除通过促进称为双霍利迪连接（dHJ）的交叉特异性 JM 的形成来促进交叉的想法。与这一想法相反，dHJ 在 exo1Δ 突变体中以野生型水平形成，这意味着 Exo1 具有促进 dHJ 解析为交叉的第二个功能。令人惊讶的是，Exo1 的 dHJ 解析功能独立于其核酸酶活性，但需要与假定的核酸内切酶复合物 Mlh1-Mlh3 相互作用。因此，减数分裂过程中 Exo1 的 DSB 切除和前交叉功能涉及时间和生化上不同的活动。
The Rad2/XPG family nuclease, Exo1, functions in a variety of DNA repair pathways. During meiosis, Exo1 promotes crossing-over and thereby facilitates chromosome segregation at the first division. Meiotic recombination is initiated by programmed DNA double-strand-breaks (DSBs). Nucleolytic resection of DSBs generates long 3′-single-strand tails that undergo strand-exchange with a homologous chromosome to form Joint Molecule (JM) intermediates. We show that meiotic DSB-resection is dramatically reduced in exo1Δ mutants and test the idea that Exo1-catalyzed resection promotes crossing-over by facilitating formation of crossover-specific JMs called double-Holliday Junctions (dHJs). Contrary to this idea, dHJs form at wild-type levels in exo1Δ mutants implying that Exo1 has a second function that promotes resolution of dHJs into crossovers. Surprisingly, the dHJ resolution function of Exo1 is independent of its nuclease activities, but requires interaction with the putative endonuclease complex, Mlh1-Mlh3. Thus, the DSB-resection and pro-crossover functions of Exo1 during meiosis involve temporally and biochemically distinct activities.
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