DOI: 10.1016/B978-0-12-378630-2.00315-7
关键词: Point mutation 、 Genetics 、 DNA mismatch repair 、 DNA repair 、 Base excision repair 、 Replication protein A 、 Immortal DNA strand hypothesis 、 Nucleotide excision repair 、 Biology 、 Mutation
摘要: Mutations, which are important for the evolution of genomes and impact disease progression, occur at similarly low rates in a variety organisms. Mammalian genomes, comprised billions nucleotides, replicated with exquisite precision during each cell cycle. The DNA mismatch repair (MMR) system serves as spell checker to correct nucleotide misincorporations that escape detection by polymerases. MMR improves fidelity replication so mutations only once ~10 9 polymerization events. In absence mutation, increased ~1000-fold. vast majority these base substitutions small insertions/deletions primarily repetitive DNA. humans, least four genes, inherited an autosomal-dominant fashion, have been implicated hereditary nonpolyposis colorectal cancer (HNPCC). Mutations genes also lead higher frequency sporadic tumors many tissue types through increases spontaneous mutations. This article provides overview mechanism mammalian cells, focusing on factors required recognition downstream steps, interactions machinery.