Testing excision models for responses of mismatch-repair systems to UV photoproducts in DNA.

摘要: Mismatch-repair (MMR) systems correct DNA replication errors and respond to a variety of lesions. Previous observations that MMR antagonizes UV mutagenesis, the mismatch-recognition protein heterodimer MSH2•MSH6 (MutSα) selectively binds containing “mismatched” photoproducts (T[CPD]T/AG, T[6-4]T/AG) but not “matched” (T[CPD]T/AA, T[6-4]T/AA), suggested mismatched would provoke excision similar bases. Excision incorrect nucleotides inserted opposite template might then prevent UV-induced mutation. We tested T[CPD]T/AG DNA, in sequence context which it is bound substantially by hMutSα three other contexts, for stimulation 3′ mammalian nuclear extracts. was inactive HeLa extracts, or extracts deficient photoproduct-binding proteins DDB XPC• hHR23B, arguing against interference from nucleotide repair pathway. Prior incubation with MLH2·PMS2 (hMutLα) did increase relative homoduplex controls. T[6-4]T/AG also failed excision. T/G, C/A, T/T substrates, even though no better than efficiently provoked Even substrate (in different contexts) significantly Thus, may suppress mutagenesis non-excisive mechanisms. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc.