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

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Cutaneous genus beta human papillomavirus (β-HPV) infections are common.
• Understanding how β-HPV manipulates host cells, especially in response to UV damage, is crucial due to constant skin exposure to UV radiation.

Purpose of the Study:

• To investigate the impact of β-HPV E6 proteins on the activation of ATM and ATR kinases and their downstream signaling pathways involved in UV DNA repair.

Main Methods:

• Assessed the activation status of ATM and ATR kinases in the presence of β-HPV E6.
• Examined the phosphorylation and accumulation of downstream targets like XPA and POLη.
• Investigated the effect on ATM-mediated phosphorylation of BRCA1.

Main Results:

• β-HPV E6 significantly decreased the activation of both ATM and ATR kinases.
• Inhibition of ATM/ATR activation led to reduced phosphorylation and accumulation of XPA, an ATR target essential for UV repair.
• β-HPV E6 hindered POLη accumulation and foci formation, critical for translesion synthesis.
• Phosphorylation of BRCA1 by ATM was also attenuated by β-HPV E6.

Conclusions:

• β-HPV E6 partially inhibits the DNA damage response pathway by reducing ATM and ATR activation.
• Despite incomplete inhibition, β-HPV 8E6's effect on ATM/ATR has functional consequences for UV repair mechanisms in host cells.