When and Where Polymerases Encounter DNA Lesions

Abstract

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 eŠects 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 eŠects among the many cell types in the human body. Most diŠerentiated 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.

An in vitro method for detecting genetic toxicity based on inhibition of RNA synthesis by DNA lesions

“…Only the combination of T7 RNAP transcription and qPCR can detect both cisplatin- and UV-induced DNA lesions that interfere with transcription. Therefore, our results support the idea analysis of transcription products can be used to detect damage in DNA templates, consistent with the model of TCR [ 7 , 25 ]. Our new method might reveal DNA lesions that cannot be detected by conventional replication-based methods and should facilitate research on DNA damage responses.…”

“…Under laboratory conditions, cell lines are maintained in an environment favorable to growth, DNA repair, prevention of apoptosis, and other aspects of cellular metabolism [ 3 , 5 – 7 ]. As cancer and stem cells divide rapidly and constantly, proper experimental conditions for such cell lines are focused on replication.…”