Mechanism of 5′-directed excision in human mismatch repair
Mechanism of 5′-directed excision in human mismatch repair
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DOI：
10.1016/s1097-2765(03)00428-3
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发表时间：
2003-11-01
期刊：
影响因子：
16
通讯作者：
Modrich, P
中科院分区：
文献类型：
--
作者：
Genschel, J;Modrich, P
我们已经开发了一个纯化的系统，支持错配依赖的5 '->3'切除。在RPA、ATP和错配的存在下，MutSalpha通过EXOI激活5 '-3'切除，并且切除在去除错配后终止。MutSa赋予EXOI高持续合成能力，终止是由于这种持续合成复合物从螺旋的RPA依赖性置换和EXOI在产物中RPA结合缺口处重新加载的能力弱，以及在不存在错配辅因子的情况下MutSalpha和MutLalpha依赖性抑制EXOI活性。如在纯化系统中观察到的，在HeLa核提取物中由5'链断裂指导的切除可以在MutL α或PCNA不存在的情况下进行，尽管提取物系统中的3'切除需要两种蛋白质。
We have developed a purified system that supports mismatch-dependent 5'-->3' excision. In the presence of RPA, ATP, and a mismatch, MutSalpha activates 5'-3' excision by EXOI, and excision terminates after removal of the mispair. MutSa confers high processivity on EXOI, and termination is due to RPA-dependent displacement of this processive complex from the helix and a weak ability of EXOI to reload at the RPA-bound gap in the product, as well as MutSalpha- and MutLalpha-dependent suppression of EXOI activity in the absence of a mismatch cofactor. As observed in the purified system, excision directed by a 5' strand break in HeLa nuclear extract can proceed in the absence of MutLalpha or PCNA, although 3' excision in the extract system requires both proteins.