Functional interactions between Sae2 and the Mre11 complex
Functional interactions between Sae2 and the Mre11 complex
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DOI：
10.1534/genetics.107.081331
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发表时间：
2008-02-01
期刊：
影响因子：
3.3
通讯作者：
Petrini, John H. J.
中科院分区：
文献类型：
--
作者：
Kim, Hee-Sook;Vijayakumar, Sangeetha;Petrini, John H. J.
Mre 11复合物在双链断裂（DSB）修复、减数分裂重组和DNA损伤检查点途径中发挥作用。Sae 2缺陷对Mre 11复合体有相反的影响。一方面，它似乎损害了Mre 11核酸酶在DNA修复和减数分裂DSB加工中的功能，另一方面，Sae 2缺陷通过Te 11-Mre 11复合物（TM）途径激活Mre 11复合物依赖的DNA损伤信号传导。我们证明，SAE 2过表达阻断TM通路，表明Sae 2拮抗Mre 11 1-复合物检查点功能。为了了解Sae 2如何调节Mre 11复合物，我们筛选了Sae 2等位基因，这些等位基因在Mre 11复合物检查点功能方面表现为无效，但保持核酸酶功能完整。这些Sae 2等位基因的表型特征表明，Sae 2作为一个多聚体的功能，并影响Mre 11核酸酶的底物特异性。我们发现Sae 2寡聚化独立于DNA损伤，并且寡聚化是其对Mre 11核酸酶和检查点功能的调节影响所必需的。
The Mre11 complex functions in double-strand break (DSB) repair, meiotic recombination, and DNA damage checkpoint pathways. Sae2 deficiency has opposing effects on the Mre11 complex. On one hand, it appears to impair Mre11 nuclease function in DNA repair and meiotic DSB processing, and on the other, Sae2 deficiency activates Mre11-complex-dependent DNA-damage-signaling via the Te11-Mre11 complex (TM) pathway. We demonstrate that SAE2 overexpression blocks the TM pathway, suggesting that Sae2 antagonizes Mre11 1-complex checkpoint functions. To understand how Sae2 regulates the Mre11 complex, we screened for sae2 alleles that behaved as the null with respect to Mre11-complex checkpoint functions, but left nuclease function intact. Phenotypic characterization of these sae2 alleles suggests that Sae2 functions as a multimer and influences the substrate specificity of the Mre11 nuclease. We show that Sae2 oligomerizes independently of DNA damage and that oligomerization is required for its regulatory influence on the Mre11 nuclease and checkpoint functions.