The frequency and structure of recombinant products is determined by the cellular level of MutL
The frequency and structure of recombinant products is determined by the cellular level of MutL
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DOI：
10.1073/pnas.0610149104
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发表时间：
2007-05-22
影响因子：
11.1
通讯作者：
Matic, Ivan
中科院分区：
文献类型：
--
作者：
Elez, Marina;Radman, Miroslav;Matic, Ivan
重复DNA序列的存在是一种基因组缺陷，因为重复序列间的重组会导致染色体重排。错配修复系统可以防止不相同重复序列之间的重组，但抗重组机制尚未建立。尽管MutS蛋白与异双工DNA中的碱基对不匹配结合，但MutS的作用。阻止重组的蛋白质是未知的。在筛选旨在确定新的细胞功能，抑制缺失的形成涉及不相同的DNA重复，我们分离出一个多功能突变体具有功能分离表型。突变体显示出缺失的频率增加，但突变的频率没有增加。分裂表型是由于MutL水平降低，表明重组而非复制编辑对Mutt高度敏感。的水平。通过改变MutL水平，我们发现产生缺失的重组频率与细胞MutL的数量呈负相关。重组重复序列的DNA序列分析表明，异双工DNA对碱基对错配的耐受性也与MutL水平呈负相关。与重组不同，错配修复对误合并错误的纠正对Mutt的波动不敏感。的水平。MutS的过量产生不会影响这两种表型，这表明，与MutL不同，MutS不限制错配修复活动。这些结果表明，MutL(1)决定了重组过程中有效的DNA同源性，(h)精细调节了涉及重复、分散DNA序列的缺失形成过程。
The presence of repeated DNA sequences is a genomic liability, because interrepeat recombination can result in chromosomal rearrangements. The mismatch repair system prevents recombination between nonidentical repeats, but the mechanism of antirecombination has not been established. Although the MutS protein binds to base pair mismatches in heteroduplex DNA, the role of the Mutt. protein in preventing recombination is unknown. In a screen designed to identify new cellular functions that suppress deletion formation involving nonidentical DNA repeats, we isolated a mutL mutant having a separation-of-function phenotype. The mutant showed an increased frequency of deletions but not of mutations. The split phenotype is due to a decreased MutL level, indicating that recombination, but not replication editing, is highly sensitive to Mutt. level. By altering the MutL level, we found that the frequency of deletion-generating recombination is inversely related to the amount of cellular MutL. DNA sequence analysis of the recombined repeats shows that the tolerance of base pair mismatches in heteroduplex DNA is also inversely correlated with MutL level. Unlike recombination, correction of misincorporation errors by mismatch repair is insensitive to fluctuations in Mutt. level. Overproduction of MutS does not affect either of these phenotypes, suggesting that, unlike MutL, MutS is not limiting for mismatch repair activities. These results indicate that MutL (1) determines effective DNA homology in recombination processes and (h) fine tunes the process of deletion formation involving repeated, diverged DNA sequences.