Preprint Article Version 1 This version is not peer-reviewed

β-HPV 8E6 Attenuates ATM and ATR Signaling in Response to UV Damage

Version 1 : Received: 27 September 2019 / Approved: 30 September 2019 / Online: 30 September 2019 (04:17:08 CEST)

How to cite: Snow, J.A.; Murthy, V.; Dacus, D.; Hu, C.; Wallace, N.A. β-HPV 8E6 Attenuates ATM and ATR Signaling in Response to UV Damage. Preprints 2019, 2019090338 (doi: 10.20944/preprints201909.0338.v1). Snow, J.A.; Murthy, V.; Dacus, D.; Hu, C.; Wallace, N.A. β-HPV 8E6 Attenuates ATM and ATR Signaling in Response to UV Damage. Preprints 2019, 2019090338 (doi: 10.20944/preprints201909.0338.v1).

Abstract

Given the high prevalence of cutaneous genus beta human papillomavirus (β-HPV) infections, it is important to understand how they are manipulating their host cells. This is particularly true for cellular responses to UV damage, since our skin is continually exposed to UV. The E6 protein from β-HPV (β-HPV E6) decreases the abundance of two essential UV-repair kinases (ATM and ATR). Since β-HPV E6 reduces their availability, the impact on downstream signaling events has been uncertain. We demonstrate that β-HPV E6 decreases ATM and ATR activation. This inhibition extended to XPA, an ATR target necessary for UV repair, lowering both its phosphorylation and accumulation. β-HPV E6 hinders POLη phosphorylation and foci formation, critical steps in translesion synthesis. ATM’s phosphorylation of BRCA1 is also attenuated by β-HPV E6. However, β-HPV E6’s hindrance of ATM/ATR signaling during UV-associated cell cycle arrest was incomplete. While there was less phosphorylation of immediate downstream targets (CHK1), events further down the cascade were not decreased. These observations are consistent with β-HPV infections making UV radiation more deleterious and support the proposed role of β-HPV in early stages of non-melanoma skin cancer development.

Subject Areas

genus beta human papillomavirus; ATM; ATR; nucleotide excision repair; translesion synthesis; cell cycle; uv

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