When and Where Polymerases Encounter DNA Lesions

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  • Kuraoka Isao
    Division of Chemistry, Graduate School of Engineering Science, Osaka University

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Although there are some similarities and dissimilarities between DNA and RNA polymerase as enzymes, when polymerase encounters a DNA lesion, the polymerase proceeds with one of two actions. One is to stall at the DNA lesion, which results in DNA repair mechanisms or cell death being induced. The other is for the polymerase to bypass the DNA lesion, which results in a mutation that could subsequently lead to carcinogenesis. The effects of DNA lesions, on either DNA polymerases or RNA polymerases, might be dependent on the cell cycle. This is because DNA polymerase in replication and RNA polymerase in transcription operate in the S phase and the G0 phase of the cell cycle in human cells, respectively. In addition, lesions may vary in their effects among the many cell types in the human body. Most differentiated cells, like cardiomyocytes and neurons, are post-mitotic, non-dividing cells. Some somatic cells, stem cells, and cancer cells are dividing cells in which DNA replication occurs in the S phase. To re-evaluate the biological risk conveyed by DNA lesions in living human cells, studies on cell-cycle-dependent actions of both DNA polymerase and RNA polymerase on DNA templates that contain lesions might be required.<br>

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