E2F mediated induction of p19INK4d plays an important role in cell cycle and DNA damage response

ABEL CARCAGNO; SILVINA SONZOGNI; JULIETA CERUTI; LUCIANA GIONO; EDUARDO CÁNEPA

Villa Carlos Paz, Córdoba, Argentina

Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

The aim of this work was to study the role of E2F in two aspects of p19 expression: its periodic regulation during the cell cycle and its induction during the DNA damage response. To achieve this, we developed a strategy based on triple helix-forming oligonucleotides (TFOs) in order to prevent E2F binding to its response elements in the p19 promoter. Proof of principle experiments showed that TFOs were able to specifically prevent p19 induction by E2F during normal cell cycle as well as following DNA damage. In subsequent experiments, TFOs transfected cells showed alterations in their cell cycle kinetics, proliferation and ability to repair damaged DNA (clonogenicity). These results highlight the significance of the regulation of p19 by E2F in different physiological situations.