Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast
Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast
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DOI：
10.1073/pnas.94.18.9757
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发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
JinksRobertson, S
中科院分区：
文献类型：
--
作者：
Datta, A;Hendrix, M;JinksRobertson, S
序列差异是同源重组的有力障碍;这种障碍大部分来自错配修复蛋白发挥的抗重组活性。反向重复序列测定系统与重组底物的同一性范围从74%到100%，已被用来定义序列分歧和有丝分裂交换率在酵母之间的关系。为了阐明错配修复机制在调节错配底物之间重组中的作用，我们在野生型和错配修复缺陷菌株中进行了实验。我们发现，一个单一的错配是足以抑制重组，否则相同的序列，这种抑制是依赖于错配修复系统。额外的错配对重组率具有累积的负面影响。随着序列差异高达约10%，错配的抑制作用主要来自错配修复系统的抗重组活性。在更高水平的分歧下，即使在不存在错配修复活性的情况下，重组也是低效的。在野生型和错配修复缺陷菌株中，重组率和序列分歧水平之间观察到近似的对数线性关系。
Sequence divergence acts as a potent barrier to homologous recombination; much of this barrier derives from an antirecombination activity exerted by mismatch repair proteins. An inverted repeat assay system with recombination substrates ranging in identity from 74% to 100% has been used to define the relationship between sequence divergence and the rate of mitotic crossing-over in yeast. To elucidate the role of the mismatch repair machinery in regulating recombination between mismatched substrates, we performed experiments in both wild-type and mismatch repair defective strains. We find that a single mismatch is sufficient to inhibit recombination between otherwise identical sequences, and that this inhibition is dependent on the mismatch repair system. Additional mismatches have a cumulative negative effect on the recombination rate. With sequence divergence of up to approximately 10%, the inhibitory effect of mismatches results mainly from antirecombination activity of the mismatch repair system. With greater levels of divergence, recombination is inefficient even in the absence of mismatch repair activity. In both wild-type and mismatch repair defective strains, an approximate log-linear relationship is observed between the recombination rate and the level of sequence divergence.