Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3

Yvette Habraken, Patrick Sung, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

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Abstract

DNA-mismatch repair removes mismatches from the newly replicated DNA strand. In humans, mutations in the mismatch repair genes hMSH2, hMLH1, hPMS1 and hPMS2 result in hereditary non-polyposis colorectal cancer (HNPCC) [1-8]. The hMSH2 (MSH for MutS homologue) protein forms a complex with a 160 kDa protein, and this heterodimer, hMutSα, has high affinity for a G/T mismatch [9,10]. Cell lines in which the 160 kDa subunit of hMutSα is mutated are specifically defective in the repair of base-base and single-nucleotide insertion/deletion mismatches [9,11]. Genetic studies in S. cerevisiae have suggested that MSH2 functions with either MSH3 or MSH6 in mismatch repair, and, in the absence of the latter two genes, MSH2 is inactive [12,13]. MSH6 encodes the yeast counterpart of the 160 kDa subunit of hMutSα [12,13]. As in humans, yeast MSH6 forms a complex with MSH2, and the MSH2-MSH6 heterodimer binds a G/F mismatch [14]. Here, we find that MSH2 and MSH3 form another stable heterodimer, and we purity this heterodimer to near homogeneity. We show that MSH2-MSH3 has low affinity for a G/T mismatch but binds to insertion/deletion mismatches with high specificity, unlike MSH2- MSH6.

Original languageEnglish (US)
Pages (from-to)1185-1187
Number of pages3
JournalCurrent Biology
Volume6
Issue number9
DOIs
StatePublished - Sep 1996

Fingerprint

DNA Mismatch Repair
Yeast
Repair
Yeasts
yeasts
DNA
colorectal neoplasms
purity
Melanocyte-Stimulating Hormones
Proteins
genes
proteins
Genes
nucleotides
cell lines
mutation
Saccharomyces cerevisiae
Colorectal Neoplasms
Nucleotides
Cell Line

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3. / Habraken, Yvette; Sung, Patrick; Prakash, Louise; Prakash, Satya.

In: Current Biology, Vol. 6, No. 9, 09.1996, p. 1185-1187.

Research output: Contribution to journalArticle

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