New Mechanistic Insights into PARP-1-mediated DNA Damage Response

Abstract

PARP-1 is a major poly(ADP-ribose) transferase that plays an important role in DNA damage repair. PARP-1 has been shown to be a DNA single-strand and double-strand break sensor protein that helps rapidly recruit many downstream DNA repair proteins to damaged DNA sites in a poly(ADP-ribose) dependent manner. In this presentation I will talk about a new mechanism of PARP-1-mediated DNA damage response. We identified and provided the biochemical and structural evidence that PARP-1 interacts with a critical protein called Timeless. We demonstrated that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1 but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. Furthermore, we show that Timeless and PARP-1 interaction is required for efficient homologous recombination repair.