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Human papillomaviruses (HPV) are small DNA viruses that cause disease in epithelial surfaces. Notably, the HPV16 type is associated with 50% of all cervical cancers. The carcinogenic potential of some of the high-risk HPV has previously been linked to an interaction of the HPV E6 protein with the tumor suppressor protein p53 which promotes p53 degradation and thereby facilitates malignant transformation.
In a recent issue of the EMBO Journal (Vol. 21 No. 17, pp. 4741-4748), Thomas Iftner and colleagues show that HPV E6 protein may also trigger genetic instability by interfering with DNA repair. The authors used the HPV8 E6 protein as a bait in a yeast two-hybrid assay to identify novel proteins with which E6 interacts. They found that the E6 proteins of HPV1, HPV8 and HPV16 bind to and inhibit the repair activity of XRCC1. The XRCC1 protein is central to DNA single-strand break repair (SSBR) where it acts as a scaffold, recruiting and modulating the enzymatic components of the DNA repair machinery. Loss of XRCC1 causes embryonic lethality in mice and mutant XRCC1 has been associated with an increase in genetic instability, a common feature in cancer. Thus, the results of Iftner et al. provide an interesting alternative explanation for the genetic instability observed in human tumors persistently infected with papillomaviruses. The authors finally discuss some hypothesises concerning the biological role of the XRCC1/E6 interaction.
Author contact:
Thomas Iftner
Universitätsklinikum Tübingen
Elfriede-Aulhorn-Strasse 6
D-72076 Tübingen, Germany
E-mail: tsiftner@med.uni-tuebingen.de
Message posted by: Ulrike Sattler
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