High-risk human papillomavirus oncogenes disrupt the Fanconi anemia DNA repair pathway by impairing localization and de-ubiquitination of FancD2
Fig 8
E6 attenuates Palb2 expression and foci formation.
(A-C) HFKs were transduced with LXSN, E6 or E6/E7 (A) Immunoblot showing Palb2 expression. Actin serves as a loading control (left panel). Graph showing relative Palb2 protein expression from 3 independently derived E6/E7 cell lines (right panel). (B) Cells were untreated or treated with cisplatin (3 uM) for 24 hr and immunostained with Palb2, pH2AX, and DAPI. Cells with >5 Palb2 foci were counted and the percentage of positive cells is plotted (n = 3, mean ± SD). * and ** indicate significance respectively at p<0.05 and p<0.01 (compared to LXSN) whereas ns indicates non-significant. (C) HFKs were transfected with siControl or siPalb2. Immunoblot confirming depletion of Palb2 (upper panel). Cisplatin survival assay for siRNA-transfected cells (lower panel).