A non-canonical mismatch repair pathway in prokaryotes.
A non-canonical mismatch repair pathway in prokaryotes.
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DOI：
10.1038/ncomms14246
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发表时间：
2017-01-27
影响因子：
16.6
通讯作者：
Blázquez J
中科院分区：
文献类型：
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作者：
Castañeda-García A;Prieto AI;Rodríguez-Beltrán J;Alonso N;Cantillon D;Costas C;Pérez-Lago L;Zegeye ED;Herranz M;Plociński P;Tonjum T;García de Viedma D;Paget M;Waddell SJ;Rojas AM;Doherty AJ;Blázquez J
错配修复（MMR）是一种几乎普遍存在的途径，对于维持基因组稳定性至关重要。 MutS 和 MutL 蛋白家族的成员执行错配校正的关键步骤。尽管这种修复途径非常重要，但几乎所有放线菌和许多古细菌中都不存在 MutS-MutL。然而，这些生物体表现出与带有 MMR 的物种相似的自发突变率和谱，这表明存在基于典型 MutS-MutL 的 MMR 的替代品。在这里，我们报道耻垢分枝杆菌 NucS/EndoMS 是一种假定的核酸内切酶，与已知的 MMR 因子没有结构同源性，它是避免突变和抗重组所必需的，这是典型 MMR 的标志。此外，对耻垢分枝杆菌替代模型中天然存在的多态性 NucS 的表型分析表明结核分枝杆菌突变菌株的存在。 NucS 的系统发育分析表明，一个复杂的进化过程导致了原核生物的分散分布模式。总之，这些发现表明 MMR 的不同途径在自然界中至少进化了两次。尽管错配修复对于基因组稳定性很重要，但许多古细菌和几乎所有放线菌都缺乏 MutS 和 MutL 蛋白。在此，作者使用耻垢分枝杆菌作为模型，报告 NucS/EndoMS 核酸内切酶在独特的错配修复途径中发挥作用。
Mismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite the major importance of this repair pathway, MutS–MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS–MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature. Despite the importance of mismatch repair for genome stability, many Archaea and almost all Actinobacteria lack MutS and MutL proteins. Here the authors, using Mycobacterium smegmatis as a model, report that NucS/EndoMS endonuclease acts in a distinct mismatch repair pathway.