The human MLH1 cDNA complements dna mismatch repair defects in Mlh1- deficient mouse embryonic fibroblasts

Andrew B. Buermeyer, Carmell Wilson-Van Patten, Sean M. Baker, R. Michael Liskay

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

The DNA mismatch repair gene hMLH1 is reported to function in mutation avoidance, cell cycle checkpoint control, the cytotoxicity of various DNA- damaging agents, and transcription-coupled nucleotide excision repair. Formal proof of the involvement of hMLH1 in these processes requires single gene complementation. We have stably expressed hMLH1 from a transfected cDNA in Mlh1-deficient mouse embryonic fibroblasts. Expression of hMLH1 restored normal levels of mPMS2 protein, reduced spontaneous base substitution and microsatellite mutations, increased sensitivity to the toxic effects of 6- thioguanine (6-TG), and restored 6-TG-induced cell cycle arrest. Our studies confirm that hMLH1 has an essential role in the maintenance of genomic stability and the potentiation of 6-TG cytotoxicity and provide a system for detailed structure/function analysis of the hMLH1 protein.

Original languageEnglish (US)
Pages (from-to)538-541
Number of pages4
JournalCancer Research
Volume59
Issue number3
StatePublished - Feb 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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