β-HPV 5 and 8 E6 Disrupt Homology Dependent Double Strand Break Repair by Attenuating BRCA1 and BRCA2 Expression and Foci Formation

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Human Papillomaviruses are a family of viruses with over 100 different members that infect mucous membranes and skin. Infections with some of these viruses are linked to cancers of the cervix and oropharynx. In this work, we explore the question of whether other members of this virus family may also contribute to skin cancer by inhibiting the ability of cells to repair the damage caused from UV exposure. Here, we build on our previous work showing that the E6 protein from two of these viruses (β-HPV 5 and 8) reduces the cellular response to UV damage by decreasing the abundance of two cellular proteins (p300 and ATR) involved in repairing the UV-damaged DNA, leading to more double strand DNA breaks following UV exposure. Here we show that the loss of p300 has further deleterious consequences, specifically that it results in diminished expression of two proteins (BRCA1 and BRCA2) involved in the repair of double strand breaks. Our data shows that this results in fewer BRCA1 and BRCA2 repair foci forming at sites of damage and ultimately in attenuated repair of these lesions. Together, this work provides further support for a link between β-HPV infections and skin cancer.

Vyšlo v časopise: β-HPV 5 and 8 E6 Disrupt Homology Dependent Double Strand Break Repair by Attenuating BRCA1 and BRCA2 Expression and Foci Formation. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004687
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004687

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