Dual Inhibitors of PARPs and ROCKs

Interferon - stimulated PARPs are

Gene Regulation: Histones, HDACs, PARPs, Ubiquitination & Sumoylation

Ubiquitination & Sumoylation C e l l C y c l e & D N A T r a n s a c t i o n s In eukaryotes, the several meters long genomic DNA needs to be packed into chromosomes with a diameter of only several hundred micrometers. This is achieved through an elaborated scheme of packaging that starts with the formation of nucleosomes from DNA winding around an octamer core of histones H2A/H2B/H3/H4, foll...

Synthetic Lethality of Cohesins with PARPs and Replication Fork Mediators

Synthetic lethality has been proposed as a way to leverage the genetic differences found in tumor cells to affect their selective killing. Cohesins, which tether sister chromatids together until anaphase onset, are mutated in a variety of tumor types. The elucidation of synthetic lethal interactions with cohesin mutants therefore identifies potential therapeutic targets. We used a cross-species...

Involvement of PARPs in cell death.

Poly(ADP-ribosylation), an NAD dependent reaction culminating in the formation of ADP-ribose monomers, and their following polymerization, is activated as an emergency process in crucial situations such as DNA damage and cellular stress; due to this crucial function, the modulation of poly(ADP-ribosylation) during cell death has been investigated. This review will describe the properties of pol...

Structural Implications for Selective Targeting of PARPs

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them at...