Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiae.
Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pone.0007488
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发表时间：
2009-10-16
期刊：
影响因子：
3.7
通讯作者：
Bailis AM
中科院分区：
文献类型：
--
作者：
Manthey GM;Naik N;Bailis AM
在暴露于导致DNA双链断裂（DSB）的物质（如电离辐射和化疗药物）的细胞中经常观察到染色体易位，并且通常与哺乳动物中的肿瘤相关。最近，易位形成的芽殖酵母，酿酒酵母，已被发现发生在高频率的多个DSB相邻的非同源染色体上的重复序列的创建。易位形成的遗传控制和含有易位的克隆的染色体互补表明易位形成通过单链退火（SSA）发生。SSA易位形成的重要因素是中心错配修复（MMR）和同源重组（HR）因子Msh2。在这里，我们描述了几个MSH2错义突变易位形成的影响，这表明MSH2具有可分离的功能，在稳定退火单链，并从其末端去除非同源序列。此外，msh2等位基因和RAD 1的无效等位基因之间的相互作用表明，Msh2阻断了去除这些序列的另一种机制，RAD 1编码一种对去除非同源尾至关重要的核酸酶亚基。这些结果表明，Msh2在急性水平的DNA损伤后染色体易位的形成中起着多种作用。
Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs), such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA). Among the factors important for translocation formation by SSA is the central mismatch repair (MMR) and homologous recombination (HR) factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage.
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