ArticleThe Journal of biological chemistry2012
Biochemical analysis of the human mismatch repair proteins hMutSα MSH2(G674A)-MSH6 and MSH2-MSH6(T1219D).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Lynch Syndrome: An Update of Underlying Molecular Mechanisms, Phenotypes and Methods to Classify Variants of Uncertain Significance.Biomedicines · 2026Review
- Article
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Article
- MSH2-MSH3 promotes DNA end resection during homologous recombination and blocks polymerase theta-mediated end-joining through interaction with SMARCAD1 and EXO1.Nucleic acids research · 2023Article
- Expression differences between proteins responsible for DNA damage repair according to the Gleason grade as a new heterogeneity marker in prostate cancer.Archives of medical science : AMS · 2023Article
- Classification of MSH6 Variants of Uncertain Significance Using Functional Assays.International journal of molecular sciences · 2021Review
- Dynamic human MutSα-MutLα complexes compact mismatched DNA.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Functional interrogation of Lynch syndrome-associated MSH2 missense variants via CRISPR-Cas9 gene editing in human embryonic stem cells.Human mutation · 2019Article
- Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer.Oncology letters · 2018Article
- The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans.PLoS biology · 2017Article
- Enhanced electrostatic force microscopy reveals higher-order DNA looping mediated by the telomeric protein TRF2.Scientific reports · 2016Article
- Mutations in the nucleotide binding and hydrolysis domains of Helicobacter pylori MutS2 lead to altered biochemical activities and inactivation of its in vivo function.BMC microbiology · 2016Article
- DNA mismatch repair and the DNA damage response.DNA repair · 2016Review
- Mismatch binding, ADP-ATP exchange and intramolecular signaling during mismatch repair.DNA repair · 2016Review
- Single-Molecule FRET to Measure Conformational Dynamics of DNA Mismatch Repair Proteins.Methods in enzymology · 2016Article
- Milestones of Lynch syndrome: 1895-2015.Nature reviews. Cancer · 2015Review
- The UvrD303 hyper-helicase exhibits increased processivity.The Journal of biological chemistry · 2014Article
- The dual nature of mismatch repair as antimutator and mutator: for better or for worse.Frontiers in genetics · 2014Review
- Mutation rates, spectra, and genome-wide distribution of spontaneous mutations in mismatch repair deficient yeast.G3 (Bethesda, Md.) · 2013Article
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8 authors at 4 institutions in 1 country.
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Abstract
The heterodimeric human MSH2-MSH6 protein initiates DNA mismatch repair (MMR) by recognizing mismatched bases that result from replication errors. Msh2(G674A) or Msh6(T1217D) mice that have mutations in or near the ATP binding site of MSH2 or ATP hydrolysis catalytic site of MSH6 develop cancer and have a reduced lifespan due to loss of the MMR pathway (Lin, D. P., Wang, Y., Scherer, S. J., Clark, A. B., Yang, K., Avdievich, E., Jin, B., Werling, U., Parris, T., Kurihara, N., Umar, A., Kucherlapati, R., Lipkin, M., Kunkel, T. A., and Edelmann, W. (2004) Cancer Res. 64, 517-522; Yang, G., Scherer, S. J., Shell, S. S., Yang, K., Kim, M., Lipkin, M., Kucherlapati, R., Kolodner, R. D., and Edelmann, W. (2004) Cancer Cell 6, 139-150). Mouse embryonic fibroblasts from these mice retain an apoptotic response to DNA damage. Mutant human MutSα proteins MSH2(G674A)-MSH6(wt) and MSH2(wt)-MSH6(T1219D) are profiled in a variety of functional assays and as expected fail to support MMR in vitro, although they retain mismatch recognition activity. Kinetic analyses of DNA binding and ATPase activities and examination of the excision step of MMR reveal that the two mutants differ in their underlying molecular defects. MSH2(wt)-MSH6(T1219D) fails to couple nucleotide binding and mismatch recognition, whereas MSH2(G674A)-MSH6(wt) has a partial defect in nucleotide binding. Nevertheless, both mutant proteins remain bound to the mismatch and fail to promote efficient excision thereby inhibiting MMR in vitro in a dominant manner. Implications of these findings for MMR and DNA damage signaling by MMR proteins are discussed.
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