Carcinogenesis, Vol. 20, No. 2, 215-220,
February 1999
© 1999 Oxford University Press
MSH3 deficiency is not sufficient for a mutator phenotype in Chinese hamster ovary cells
Departments of Oncological Sciences and Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
In the yeast Saccharomyces cerevisiae, the mutS homolog protein products MSH3 and MSH6, each in cooperation with MSH2, play well-defined and specific roles in the repair of DNA mismatches and nucleotide loops. The discrete functions of the human homologs hMSH3 and hMSH6 are less clear and current evidence suggests that the substrate specificity of these proteins may be less strict. To determine the role of MSH3 in mammalian mismatch repair, we employed MSH3-deficient Chinese hamster ovary (CHO) cell lines. No significant changes in mutation rate were detected in the MSH3-deficient strain and there were no differences in sensitivity to DNA-damaging agents. Further analysis of hprt mutants did not show a MSH3-dependent shift in the mutant spectrum. Interestingly, thorough examination of four dinucleotide microsatellite regions revealed instability at only one locus in one of the MSH3-deficient cell lines. These data support the idea of a high degree of redundancy in the function of the MutS homologs MSH3 and MSH6, at least with respect to the control of microsatellite instability.
Abbreviations: CHO, Chinese hamster ovary; HNPCC, hereditary non-polyposis colon cancer; IR, ionizing radiation; MEM, minimum essential medium; RT–PCR, reverse transcriptase–polymerase chain reaction; SDS, sodium dodecyl sulfate; UV, ultraviolet.
1 To whom correspondence should be addressed Email: mark.meuth{at}genetics.utah.edu
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