Oxidative stress stimulates p19INK4d recruitment chromatin

LAURA BELLUSCIO; SILVIAN V. SONZOGNI; MARÍA F. OGARA; JUAN PABLO RADICELLA; EDUARDO T. CÁNEPA

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Exposure of mammalian cells to potassium bromate (KBrO3) generates oxidative DNA modifications, in particular 7, 8-dihydro- 8-oxoguanine (8-oxoG), an oxidized form of guanine, which is highly mutagenic due to its capacity to pair with adenine during replication. Previous work in our laboratory has shown that p19 participates in the DNA damage response (DDR). Although its mechanism of action is still unknown, preliminary evidence suggests that p19 might interact with chromatin and facilitate the access of the repair machinery to sites of damaged DNA. Treatment of HEK293 and SH-SY5Y cells with the DNA damaging agent KBrO3 caused an increase in p19 expression. Moreover, upon DNA damage, p19, which is mostly cytoplasmic in normal cells, translocated to the nucleus and was found associated to chromatin. This interaction resisted detergent extraction indicating that p19 is tightly bound to chromatin after DNA damage. This chromatin fraction was enriched in acetylated histones and RNAPolII suggesting that p19 preferentially interacts with euchromatin. Finally, the access of the enzyme XbaI to a chromatinized plasmid was enhanced when it was incubated with an extract from cells overexpressing p19. Taken together, these results suggest a role for p19 as a chromatin accessibility factor during the DNA damage response