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Identification of hMutLβ, a Heterodimer of hMLH1 and hPMS1
Open accessAbstract
hMLH1 and hPMS2 function in postreplicative mismatch repair in the form of a heterodimer referred to as hMutLalpha. Tumors or cell lines lacking this factor display mutator phenotypes and microsatellite instability, and mutations in the hMLH1 and hPMS2 genes predispose to hereditary non-polyposis colon cancer. A third MutL homologue, hPMS1, has also been reported to be mutated in one cancer-prone kindred, but the protein encoded by this locus has so far remained without function. We now show that hPMS1 is expressed in human cells and that it interacts with hMLH1 with high affinity to form the heterodimer hMutLbeta. Recombinant hMutLalpha and hMutLbeta, expressed in the baculovirus system, were tested for their activity in an in vitro mismatch repair assay. While hMutLalpha could fully complement extracts of mismatch repair-deficient cell lines lacking hMLH1 or hPMS2, hMutLbeta failed to do so with any of the different substrates tested in this assay. The involvement of the latter factor in postreplicative mismatch repair thus remains to be demonstrated.
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Cites
Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair
Marsischky, G. T., Filosi, N., Kane, M. F., & Kolodner, R. (1996) · Genes & Development · doi:10.1101/gad.10.4.407 · Cited by 581
Cited by
The multifaceted mismatch-repair system
Jiricny, J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1907 · Cited by 1,370
Self-citationDNA Mismatch Repair: Functions and Mechanisms
Iyer, R. R., Pluciennik, A., Burdett, V., & Modrich, P. L. (2006) · Chemical Reviews · doi:10.1021/cr0404794 · Cited by 905
DNA repair mechanisms in dividing and non-dividing cells
Iyama, T., & Wilson, D. M. (2013) · DNA Repair · doi:10.1016/j.dnarep.2013.04.015 · Cited by 697
DNA MISMATCH REPAIR AND GENETIC INSTABILITY
Harfe, B. D., & Jinks-Robertson, S. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.359 · Cited by 608
Modulation of mismatch repair and genomic stability by miR-155
Valeri, N., Gasparini, P., Fabbri, M., Braconi, C., Veronese, A., Lovat, F., Adair, B., Vannini, I., Fanini, F., Bottoni, A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002472107 · Cited by 349
Metadata
- Authors
- Räschle, M., Marra, G., Nyström-Lahti, M., Schär, P., & Jiricny, J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 274
- Issue
- 45
- Pages
- 32368-32375
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2024908018
- Cited by
- 189
- References
- 1
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Räschle, M., Marra, G., Nyström-Lahti, M., Schär, P., & Jiricny, J. (1999). Identification of hMutLβ, a Heterodimer of hMLH1 and hPMS1. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.45.32368
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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