OXIDATIVE STRESS STIMULATES p19INK4D RECRUITMENT TO CHROMATIN

BELLUSCIO L; SONZOGNI S. V.; OGARA M.F.; RADICELLA J.P.; CÁNEPA, E.T.

Puerto Madryn

Congreso; XLVI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR (SAIB); 2010

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR (SAIB)

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 ishighly mutagenic due to its capacity to pair with adenine duringreplication. Previous work in our laboratory has shown that p19participates in the DNA damage response (DDR). Although itsmechanism of action is still unknown, preliminary evidencesuggests that p19 might interact with chromatin and facilitate theaccess of the repair machinery to sites of damaged DNA.Treatment of HEK293 and SH-SY5Y cells with the DNA damagingagent KBrO3 caused an increase in p19 expression. Moreover, uponDNA 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 istightly bound to chromatin after DNA damage. This chromatinfraction was enriched in acetylated histones and RNAPolIIsuggesting that p19 preferentially interacts with euchromatin.Finally, the access of the enzyme XbaI to a chromatinized plasmidwas enhanced when it was incubated with an extract from cellsoverexpressing p19.Taken together, these results suggest a role for p19 as a chromatinaccessibility factor during the DNA damage response