Human JC virus small tumour antigen inhibits nucleotide excision repair and sensitises cells to DNA-damaging agents

Jau Ling Huang, Chang Shen Lin, Chia Chu Chang, Yu Ning Lu, Yu Ling Hsu, Tzyy Yue Wong, Yu Fei Wang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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 (PP2A) inhibitor okadaic acid on NER was similar to that of the ST, which is a PP2A-binding protein. Therefore, the deactivation of the PP2A might underlie ST-mediated NER inhibition. The results of this study indicate that exposing JCV ST-positive cells to DNA-damaging agents causes genomic instability, which contributes to carcinogenesis. Our data provide further evidence on the association between the JCV ST and human cancer.

Original languageEnglish
Pages (from-to)475-485
Number of pages11
JournalMutagenesis
Volume30
Issue number4
DOIs
Publication statusPublished - 2015 Jul 1

All Science Journal Classification (ASJC) codes

  • Genetics
  • Toxicology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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