Human JC virus small tumour antigen inhibits nucleotide excision repair and sensitises cells to DNA-damaging agents
Abstract
The human JC virus (JCV) is potentially carcinogenic to humans as a Group 2B carcinogen, and it is ubiquitous in human populations. To investigate whether the small tumour (ST) antigen of the JCV contributes to genomic instability, we established cell lines stably expressing the JCV ST and examined its role in DNA repair. Results from host cell reactivation (HCR) assay revealed that the established cell lines exhibited lower nucleotide excision repair (NER) activity than the vector control cells did. The presence of γ-H2AX, a marker of DNA damage, indicated that the established cell line contained more DNA damage foci compared with vector control cells. Furthermore, the results of clonogenic analyses indicated that the JCV ST-expressing cells were more sensitive than the vector control cells to ultraviolet (UV) irradiation and cisplatin treatment. Micronuclei formation assay revealed that the JCV ST-positive cells presented more chromosomal breakages than did the JCV ST-negative cells, particularly after exposure to DNA-damaging agents. The xeroderma pigmentosum Group D protein, a DNA helicase involved in NER, was downregulated in the JCV ST-positive cells in response to UV irradiation. The effect of the protein phosphatase 2A ...Continue Reading
References
JC virus large T-antigen and IGF-I signaling system merge to affect DNA repair and genomic integrity
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