Identification of Exo1-Msh2 interaction motifs in DNA mismatch repair and new Msh2-binding partners.

Identification of Exo1-Msh2 interaction motifs in DNA mismatch repair and new Msh2-binding partners.
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DOI:
10.1038/s41594-018-0092-y
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发表时间:
2018-08
影响因子:
16.8
通讯作者:
Kolodner RD
Kolodner RD
中科院分区:
生物学1区
文献类型:
--
作者:
Goellner EM;Putnam CD;Graham WJ 5th;Rahal CM;Li BZ;Kolodner RD

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真核细胞DNA错配修复(MMR)包括外切酶1(Exo1)依赖和非依赖途径。我们发现酿酒酵母Exo1的非结构C末端结构域在MLH1相互作用多肽(MIP)盒下游含有两个Msh2相互作用多肽(SHIP)盒。这三个位点在体内依赖于Exo1的MMR中是多余的,可以被N端-Exo1-MSH6融合蛋白所取代。SHIP-Msh2相互作用可被MSH2-M470I突变所消除,野生型而不是突变型SHIP多肽在体外可消除依赖于Exo1的MMR。我们鉴定了两个酿酒酵母Ship Box蛋白和三个候选的人Ship Box蛋白。其中,Fun30在体内依赖于Exo1的MMR中起到了很小的作用。在体内,RSC复合体既作用于Exo1依赖的MMR,也作用于Exo1非依赖的MMR。我们的结果发现了两种Exo1募集模式和一个介导Msh2与其他蛋白质相互作用的多肽模块,并支持一个模型,即Exo1在MMR中发挥作用与Msh2-MSH6复合体有关。
Eukaryotic DNA mismatch repair (MMR) involves both Exonuclease 1 (Exo1)-dependent and -independent pathways. We found that the unstructured C-terminal domain of Saccharomyces cerevisiae Exo1 contains two Msh2-Interacting-Peptide (SHIP) boxes downstream from the Mlh1-Interacting-Peptide (MIP) box. These three sites were redundant in Exo1-dependent MMR in vivo and could be replaced by an N-terminal-Exo1-Msh6 fusion protein. The SHIP-Msh2 interactions were eliminated by the msh2-M470I mutation and wild-type but not mutant SHIP peptides eliminated Exo1-dependent MMR in vitro. We identified two S. cerevisiae SHIP box-containing proteins and three candidate human SHIP box-containing proteins. One of these, Fun30, played a small role in Exo1-dependent MMR in vivo. The Rsc complex acted in both Exo1-dependent and Exo1-independent MMR in vivo. Our results identified two modes of Exo1 recruitment and a peptide module that mediates interactions between Msh2 and other proteins, and support a model in which Exo1 functions in MMR tethered to the Msh2-Msh6 complex.
Biopython:用于计算分子生物学和生物信息学的免费 Python 工具。
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