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Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs.
Open accessAbstract
Hypermutable H6 colorectal tumor cells are defective in strand-specific mismatch repair and bear defects in both alleles of the hMLH1 gene. We have purified to near homogeneity an activity from HeLa cells that complements H6 nuclear extracts to restore repair proficiency on a set of heteroduplex DNAs representing the eight base-base mismatches as well as a number of slipped-strand, insertion/deletion mispairs. This activity behaves as a single species during fractionation and copurifies with proteins of 85 and 110 kDa. Microsequence analysis demonstrated both of these proteins to be homologs of bacterial MutL, with the former corresponding to the hMLH1 product and the latter to the product of hPMS2 or a closely related gene. The 1:1 molar stoichiometry of the two polypeptides and their hydrodynamic behavior indicate formation of a heterodimer, which we have designated hMutL alpha. These observations indicate that interactions between members of the family of human MutL homologs may be restricted.
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Cited by
Mechanisms of DNA damage, repair, and mutagenesis
Chatterjee, N., & Walker, G. C. (2017) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22087 · Cited by 2,039
DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis
Roos, W. P., & Kaina, B. (2013) · Cancer Letters · doi:10.1016/j.canlet.2012.01.007 · Cited by 879
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
Mismatch repair and DNA damage signalling
Stojic, L., Brun, R., & Jiricny, J. (2004) · DNA Repair · doi:10.1016/j.dnarep.2004.06.006 · Cited by 396
Pinto, R. M., Dragileva, E., Kirby, A., Lloret, A., Lopez, E., St. Claire, J., Panigrahi, G. B., Hou, C., Holloway, K., Gillis, T., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003930 · Cited by 250
“In essence, repair of single base mismatch (G-T) substrate containing a 5 9 nick was assessed using HeLa or MutL a -deficient HCT116 [89] nuclear protein extracts (100 ng) complemented with equal amounts of purified MutL a protein complexes: hMLH1.”
MethodSelf-citationNarayanan, L., Fritzell, J. A., Baker, S. M., Liskay, R. M., & Glazer, P. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.3122 · Cited by 152
Metadata
- Authors
- Li, G. M., & Modrich, P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1995-03-14
- Volume
- 92
- Issue
- 6
- Pages
- 1950-1954
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2085315842
- Cited by
- 409
- References
- 0
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- green
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