Nse1-dependent recruitment of Smc5/6 to lesion-containing loci contributes to the repair defects of mutant complexes.
Nse1-dependent recruitment of Smc5/6 to lesion-containing loci contributes to the repair defects of mutant complexes.
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DOI：
10.1091/mbc.e11-03-0272
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发表时间：
2011-12
影响因子：
3.3
通讯作者：
O'Connell MJ
中科院分区：
文献类型：
--
作者：
Tapia-Alveal C;O'Connell MJ
The Smc5/6 complex is widely believed to be required for homologous recombination. It is shown that repair defects of Smc5/6 mutants are due to the Nse1-dependent recruitment of dysfunctional complexes to lesions. Of the three structural maintenance of chromosomes (SMC) complexes, Smc5/6 remains the most poorly understood. Genetic studies have shown that Smc5/6 mutants are defective in homologous recombination (HR), and consistent with this, Smc5/6 is enriched at lesions. However, Smc5/6 is essential for viability, but HR is not, and the terminal phenotype of null Smc5/6 mutants is mitotic failure. Here we analyze the function of Nse1, which contains a variant RING domain that is characteristic of ubiquitin ligases. Whereas deletion of this domain causes DNA damage sensitivity and mitotic failure, serine mutations in conserved cysteines do not. However, these mutations suppress the DNA damage sensitivity of Smc5/6 hypomorphs but not that of HR mutants and remarkably decrease the recruitment of Smc5/6 to loci containing lesions marked for HR-mediated repair. Analysis of DNA repair pathways in suppressed double mutants suggests that lesions are channeled into recombination-dependent and error-free postreplication repair. Thus the HR defect in Smc5/6 mutants appears to be due to the presence of dysfunctional complexes at lesions rather than to reflect an absolute requirement for Smc5/6 to complete HR.
