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| Genomic DNA is continuously subjected to damage by internal and external agents. The DNA lesions produced interfere with replication and with gene expression and they must be removed by DNA repair enzymes in order to enable proper function of DNA. When unrepaired lesions are replicated, they give rise to mutations. A broad class of DNA lesions interrupt DNA replication, leading to the formation of single-stranded regions. The emergency strategy adopted for such cases is to repair (fill in) the gap without removing the damaged base. The second strategy consists of filling-in of the gap lesion by a DNA polymerase. This mechanism is mutagenic because polymerases tend to incorporate incorrect nucleotides opposite DNA lesions. This process is under tight regulation by the SOS stress response. In addition to this mutagenesis process, a mutator activity is induced under SOS conditions, which produces mutations in the apparent absence of DNA damage (untargeted mutagenesis). In the present invention, UmuC is found to be a translesion replication DNA polymerase which replicates through a DNA lesion of damaged DNA molecule and which is found to be highly mutagenic during in vitro gap-filling replication. A method for replicating a DNA molecule with DNA lesion damage and a method for mutagenesis of a DNA molecule are provided.present relates replication damaged DNA mutagenesis mutagenic |
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