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Impaired nucleotide excision repair in UV-irradiated human oral keratinocytes immortalized with type 16 human papillomavirus genome

Oncogene volume 18, pages 6997–7001 (1999)Cite this article

Abstract

We previously reported that `high risk' human papillomaviruses (HPV) induce genetic instability in human oral keratinocytes. To understand the mechanisms of HPV-induced genetic instability, we determined the nucleotide excision repair (NER) capacity of normal (NHOK) and human papillomavirus type-16 immortalized oral keratinocytes (HOK-16B) by strand-specific removal of UV-induced cyclobutane pyrimidine dimers (CPDs) from a 16 Kb fragment of the p53 gene. In NHOK the NER activity was initiated in both DNA strands immediately, although the process in the non-transcribed strand was notably slower than that of the transcribed strand. In HOK-16B cells the initiation of CPDs removal was delayed for at least 8 h in both DNA strands, and the process was significantly slower than that in NHOK. UV-irradiation enhanced the p53 protein level more than 30-fold in NHOK, but it did not significantly alter the protein level in the HOK-16B cells. UV-irradiation also increased the p21WAF1/CIP1 protein level only in NHOK. These data indicate that `high risk' HPV induces genetic instability by impairing NER capacity of cells. Impaired NER activity of HOK-16B cells may be implicated with their inability to enhance active p53 when challenged by genotoxic stress.

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Acknowledgements

We would like to thank Marcel A Baluda and Bradley Ackerson for critical reading of this manuscript. This work was, in part, supported by grants DE11229 and DE10598 from the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

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  1. UCLA School of Dentistry, Los Angeles, 90095-1668, California, CA, USA

    Osvaldo Rey, Sora Lee & No-Hee Park

  2. Dental Research Institute, Los Angeles, 90095-1668, California, CA, USA

    Osvaldo Rey & No-Hee Park

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  1. Osvaldo Rey
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Rey, O., Lee, S. & Park, NH. Impaired nucleotide excision repair in UV-irradiated human oral keratinocytes immortalized with type 16 human papillomavirus genome. Oncogene 18, 6997–7001 (1999). https://doi.org/10.1038/sj.onc.1203180

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