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真核生物DNA错配修复

Eukaryotic DNA mismatch repair.

作者信息

Kolodner R D, Marsischky G T

机构信息

Ludwig Institute for Cancer Research, Department of Medicine and CancerCenter, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0660, USA. rkolodner@ucsd. edu.

出版信息

Curr Opin Genet Dev. 1999 Feb;9(1):89-96. doi: 10.1016/s0959-437x(99)80013-6.

Abstract

Eukaryotic mismatch repair (MMR) has been shown to require two different heterodimeric complexes of MutS-related proteins: MSH2-MSH3 and MSH2-MSH6. These two complexes have different mispair recognition properties and different abilities to support MMR. Alternative models have been proposed for how these MSH complexes function in MMR. Two different heterodimeric complexes of MutL-related proteins, MLH1-PMS1 (human PMS2) and MLH1-MLH3 (human PMS1) also function in MMR and appear to interact with other MMR proteins including the MSH complexes and replication factors. A number of other proteins have been implicated in MMR, including DNA polymerase delta, RPA (replication protein A), PCNA (proliferating cell nuclear antigen), RFC (replication factor C), Exonuclease 1, FEN1 (RAD27) and the DNA polymerase delta and epsilon associated exonucleases. MMR proteins have also been shown to function in other types of repair and recombination that appear distinct from MMR. MMR proteins function in these processes in conjunction with components of nucleotide excision repair (NER) and, possibly, recombination.

摘要

真核生物错配修复(MMR)已被证明需要MutS相关蛋白的两种不同异二聚体复合物:MSH2-MSH3和MSH2-MSH6。这两种复合物具有不同的错配识别特性和支持MMR的不同能力。关于这些MSH复合物如何在MMR中发挥作用,已经提出了多种不同的模型。MutL相关蛋白的两种不同异二聚体复合物,MLH1-PMS1(人类PMS2)和MLH1-MLH3(人类PMS1)也在MMR中发挥作用,并且似乎与包括MSH复合物和复制因子在内的其他MMR蛋白相互作用。许多其他蛋白质也与MMR有关,包括DNA聚合酶δ、RPA(复制蛋白A)、PCNA(增殖细胞核抗原)、RFC(复制因子C)、核酸外切酶1、FEN1(RAD27)以及与DNA聚合酶δ和ε相关联的核酸外切酶。MMR蛋白也已被证明在其他类型的修复和重组中发挥作用,这些修复和重组似乎与MMR不同。MMR蛋白与核苷酸切除修复(NER)的成分以及可能的重组成分一起在这些过程中发挥作用。

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