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• W2022700742 startingPage "448" @default.
• W2022700742 abstract "Saccharomyces cerevisiae MutLalpha is a heterodimer of Mlh1 and Pms1 that participates in DNA mismatch repair (MMR). Both proteins have weakly conserved C-terminal regions (CTDs), with the CTD of Pms1 harboring an essential endonuclease activity. These proteins also have conserved N-terminal domains (NTDs) that bind and hydrolyze ATP and bind to DNA. To better understand Pms1 functions and potential interactions with DNA and/or other proteins, we solved the 2.5A crystal structure of yeast Pms1 (yPms1) NTD. The structure is similar to the homologous NTDs of Escherichia coli MutL and human PMS2, including the site involved in ATP binding and hydrolysis. The structure reveals a number of conserved, positively charged surface residues that do not interact with other residues in the NTD and are therefore candidates for interactions with DNA, with the CTD and/or with other proteins. When these were replaced with glutamate, several replacements resulted in yeast strains with elevated mutation rates. Two replacements also resulted in NTDs with decreased DNA binding affinity in vitro, suggesting that these residues contribute to DNA binding that is important for mismatch repair. Elevated mutation rates also resulted from surface residue replacements that did not affect DNA binding, suggesting that these conserved residues serve other functions, possibly involving interactions with other MMR proteins." @default.
• W2022700742 created "2016-06-24" @default.
• W2022700742 creator A5006937705 @default.
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• W2022700742 creator A5024209071 @default.
• W2022700742 creator A5054055369 @default.
• W2022700742 creator A5082173620 @default.
• W2022700742 date "2010-04-01" @default.
• W2022700742 modified "2023-09-30" @default.
• W2022700742 title "Functional residues on the surface of the N-terminal domain of yeast Pms1" @default.
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• W2022700742 doi "https://doi.org/10.1016/j.dnarep.2010.01.010" @default.
• W2022700742 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2856611" @default.
• W2022700742 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20138591" @default.
• W2022700742 hasPublicationYear "2010" @default.
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