Mutator Phenotype of MUTYH-null Mouse Embryonic Stem Cells
作者： Seiki Hirano , Yohei Tominaga , Akimasa Ichinoe , Yasuhiro Ushijima , Daisuke Tsuchimoto
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摘要: To evaluate the antimutagenic role of a mammalian mutY homolog, namely Mutyh gene, which encodes adenine DNA glycosylase excising misincorporated opposite 8-oxoguanine in template DNA, we generated MUTYH-null mouse embryonic stem (ES) cells. In cells carrying no activity, spontaneous mutation rate increased 2-fold comparison with wild type The expression mMUTYH or mutant protein amino acid substitutions at proliferating cell nuclear antigen binding motif restored rates ES to level. an substitution (G365D) that corresponds germ-line (G382D) found patients multiple colorectal adenomas could not suppress elevated Although recombinant mMUTYH(G365D) purified from Escherichia coli had substantial level activity as did MUTYH, was detected expressing protein. human MUTYH gene is therefore likely be responsible for occurrence mutator phenotype these patients.
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