UNRAVELLING THE INTERPLAY BETWEEN

SIRKIN, PABLO F; CARCAGNO, ABEL F; CERUTI, JULIETA M; CÁNEPA, EDUARDO

Rosario, Argentina

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2006

SAIB

INK4 proteins are a family of CDK inhibitors that regulate the progression through the cell cycle. Among them, p19INK4d has been implicated in DNA repair, but the mechanisms by which this protein exerts this new function remain elusive. It has been shown that p19 is induced in cells irradiated with the DNA damaging agent UVC. However, transfection of BHK cells with UVC damaged DNA is not enough to achieve its induction. It is also known that DNA lesions lead to changes in chromatin structure, so we wondered if these rearrangement in chromatin organization might be the stimulus that triggers p19 induction upon DNA damage. Treatment of BHK cells with chloroquine or TSA, both chromatin modifiers, specifically induced the expression of p19. Then, we wanted to analyze the role p19 might have on chromatin structure, in an effort to explain what the function of this protein is in DNA repair. In vitro DNA repair assays show that a nuclear extract enriched in p19 is more capable of repairing a reconstituted damaged DNA template than one in which p19 has not been overexpressed. Nevertheless, this difference is not seen when the extracts are incubated in the presence of a naked template, suggesting that p19 might actually be involved in making chromatin more accessible during the DNA repair process. Together these results point to a bidirectional regulation existing between chromatin and p19.