PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance

M Rose, JT Burgess, K O'Byrne, DJ Richard… - Frontiers in cell and …, 2020 - frontiersin.org
The Poly (ADP-ribose) polymerase (PARP) family has many essential functions in cellular
processes, including the regulation of transcription, apoptosis and the DNA damage …

The multifaceted roles of PARP1 in DNA repair and chromatin remodelling

A Ray Chaudhuri, A Nussenzweig - Nature reviews Molecular cell …, 2017 - nature.com
Cells are exposed to various endogenous and exogenous insults that induce DNA damage,
which, if unrepaired, impairs genome integrity and leads to the development of various …

Poly (ADP-ribosyl) ation by PARP1: reaction mechanism and regulatory proteins

EE Alemasova, OI Lavrik - Nucleic acids research, 2019 - academic.oup.com
Abstract Poly (ADP-ribosyl) ation (PARylation) is posttranslational modification of proteins by
linear or branched chains of ADP-ribose units, originating from NAD+. The central enzyme …

Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance

SJ Pettitt, DB Krastev, I Brandsma, A Dréan… - Nature …, 2018 - nature.com
Although PARP inhibitors (PARPi) target homologous recombination defective tumours,
drug resistance frequently emerges, often via poorly understood mechanisms. Here, using …

Structural basis for potency and promiscuity in poly (ADP-ribose) polymerase (PARP) and tankyrase inhibitors

AG Thorsell, T Ekblad, T Karlberg… - Journal of medicinal …, 2017 - ACS Publications
Selective inhibitors could help unveil the mechanisms by which inhibition of poly (ADP-
ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 …

Updated protein domain annotation of the PARP protein family sheds new light on biological function

MJ Suskiewicz, D Munnur, Ø Strømland… - Nucleic Acids …, 2023 - academic.oup.com
AlphaFold2 and related computational tools have greatly aided studies of structural biology
through their ability to accurately predict protein structures. In the present work, we explored …

ADP-ribosylation, a multifaceted posttranslational modification involved in the control of cell physiology in health and disease

B Lüscher, M Bütepage, L Eckei, S Krieg… - Chemical …, 2018 - ACS Publications
Posttranslational modifications (PTMs) regulate protein functions and interactions. ADP-
ribosylation is a PTM, in which ADP-ribosyltransferases use nicotinamide adenine …

Structural basis of detection and signaling of DNA single-strand breaks by human PARP-1

S Eustermann, WF Wu, MF Langelier, JC Yang… - Molecular cell, 2015 - cell.com
Summary Poly (ADP-ribose) polymerase 1 (PARP-1) is a key eukaryotic stress sensor that
responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic …

PARP-1 activation requires local unfolding of an autoinhibitory domain

JM Dawicki-McKenna, MF Langelier, JE DeNizio… - Molecular cell, 2015 - cell.com
Summary Poly (ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational
modification PAR from substrate NAD+ to regulate multiple cellular processes. DNA breaks …

Coordination of DNA single strand break repair

R Abbotts, DM Wilson III - Free Radical Biology and Medicine, 2017 - Elsevier
The genetic material of all organisms is susceptible to modification. In some instances, these
changes are programmed, such as the formation of DNA double strand breaks during …