La charla, cuyo tìtulo es "DNA-damage sensor: PARP3 activation in the chromatin environment", se llevará a cabo el lunes 19 de diciembre a las 11 hs. en sala de seminarios IHEM (PB).

A continuación, un abstract de su charla:

PARP — poly-(ADP ribose) polymerase — constitute a family of enzymes that catalyse ADP-ribosylation of other proteins and facilitate the repair of the DNA. During the last two decades clinical trials have produced promising data for the use of PARP inhibitors in the treatment of breast, ovarian and other cancers. The key to the success of this inhibitors, is its low toxicity in healthy cells along with its remarkable efficacy against tumours with mutations in homologous recombination pathway. Most of the PARP inhibitors block the poly-(ADP-ribose) polymerases PARP1, PARP2 and PARP3, which are activated by a range of DNA strand nicks, breaks and distortions.  It was thought that these three enzymes had overlapping or degenerate roles in DNA repair. However, recent evidence, shows that the three DNA-dependent PARPs may have distinct roles. Thus, targeting the specific function of individual PARPs has the potential to enhance efficacy and reduce side effects in cancer patients.
I will focus in the most recently characterised member of this family, PARP3, which participates in the repair of chromosomal DNA single-strand breaks. We show that nicks in naked DNA stimulate PARP3 autoribosylation, but also that nicks in mononucleosomes promote trans-ribosylation of this histone target. Furthermore, PARP3 accelerates the repair of chromosomal radiation-induced single-strand DNA breaks in cells and PARP3 deficiency sensitizes them to radiation. These data let us to identify the sensing mechanism of PARP3 of damaged DNA and establish it as a molecular sensor of nicked nucleosomes.