Activation of DNA damage repair factors in HPV positive oropharyngeal cancers

Takeyuki Kono, Paul Hoover, Kate Poropatich, Tatjana Paunesku, Bharat B. Mittal, Sandeep Samant, Laimonis A. Laimins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The mechanisms regulating viral pathogenesis of human papillomavirus (HPV) associated oropharyngeal squamous cell cancers (OPSCC) are not well understood. In the cervix, activation of DNA damage repair pathways is critical for viral replication but little is known about their role in OPSCC. APOBEC factors have been shown to be increased in OPSCC but the significance of this is unclear. We therefore examined activation of DNA damage and APOBEC factors in HPV-induced OPSCC. Our studies show significantly increased levels of pCHK1, FANCD2, BRCA1, RAD51, pSMC1 and γH2AX foci in HPV-positive samples as compared to HPV-negative while the ATM effector kinase, pCHK2, was not increased. Similar differences were observed when the levels of proteins were examined in OPSCC cell lines. In contrast, the levels of APOBEC3B and 3A were found to be similar in both HPV-positive and -negative OPSCC. Our studies suggest members of ATR pathway and FANCD2 may be important in HPV-induced OPSCC.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalVirology
Volume547
DOIs
StatePublished - Aug 2020

Funding

LAL was supported by grants from the National Cancer Institute ( RO1CA 059655 and RO1CA142861 ). The research was partially supported by grants from Walter Newman family and IDP Foundation .

Keywords

  • APOBEC3A
  • APOBEC3B
  • ATR
  • DNA damage
  • FANCD2
  • HPV
  • Head and neck cancer

ASJC Scopus subject areas

  • Virology

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