Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomaviruses types 5 and 18.
Ultraviolet (UV) irradiation is a major mutagenic environmental agent, causing the appearance of DNA adducts that, if unrepaired, may give rise to mutations. Ultraviolet radiation has been indicated as a major risk factor in the development of nonmelanoma skin cancers; however, recent reports have suggested that infections with human papillomaviruses, a widespread family of epitheliotropic DNA viruses, may also contribute to the tumorigenic process. Here, we investigated whether expression of the E6 protein from different HPV types interfere with the repair of thymine dimers caused by UV-B radiation. Results show that unrepaired DNA damage can be observed in UV-B-irradiated cells expressing the E6 protein of HPV types found in cervical and epithelial cancers. Moreover, such cells have the ability to overcome the G(1) cell cycle checkpoint induced as a result of unrepaired DNA.
Giampieri
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S
Skin Tumour Laboratory, Cancer Research UK, Centre for Cutaneous Research, 2 Newark Street, London E1 2AT, UK.
Storey
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A
D002460:Cell Line; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling; D006801:Humans; D007399:Interphase; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D027383:Papillomaviridae / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology / Q000821:virology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D018736:DNA Adducts; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C487708:E6 protein, human papillomavirus type 5; D009856:Oncogene Proteins, Viral