Effects of DNA Lesions on Transcription Elongation by RNA Polymerases

概要

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A DNA molecule is vulnerable to many types of DNA-damaging agents of both endogenous and exogenous origins. To date, the majority of DNA repair and mutagenesis studies are based on the actions of DNA polymerases during the replication process. The presence of DNA lesions interferes not only with replication but also with transcription. Therefore, to provide an accurate estimate risk of damaged DNA in living cells, it is an essential factor to understand the behavior of transcription elongation complexes on the transcribed strand containing DNA lesions, which are induced by mutagens and carcinogens in the environment. Notably, the vast majority of cells living outside the artificial environment in growth factor-enriched media cannot continue to grow. Although such cells do not replicate their genome DNA, they only need to transcribe a large number of genes accurately to produce the necessary proteins for normal physiological processes. In this review, we describe the mechanism of RNA polymerases (RNAPs) stalled at DNA lesions, which is an implication of transcription-coupled nucleotide excision repair. The mutant transcripts derived from translesion RNA synthesis of RNAPs implicate the occurrence of transcriptional mutagenesis. The biological risks of DNA lesions induced by mutagens and carcinogens with regard to transcription elongation are discussed.
日本環境変異原学会の論文
2008-08-20