AUTHOR=Zhu Tao , Zheng Ju-Yan , Huang Ling-Ling , Wang Yan-Hong , Yao Di-Fei , Dai Hai-Bin 

TITLE=Human PARP1 substrates and regulators of its catalytic activity: An updated overview

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1137151

DOI=10.3389/fphar.2023.1137151

ISSN=1663-9812

ABSTRACT=<p>Poly (ADP-ribose) polymerase 1 (PARP1) is a key DNA damage sensor that is recruited to damaged sites after DNA strand breaks to initiate DNA repair. This is achieved by catalyzing attachment of ADP-ribose moieties, which are donated from NAD<sup>+</sup>, on the amino acid residues of itself or other acceptor proteins. PARP inhibitors (PARPi) that inhibit PARP catalytic activity and induce PARP trapping are commonly used for treating <italic>BRCA1/2</italic>-deficient breast and ovarian cancers through synergistic lethality. Unfortunately, resistance to PARPi frequently occurs. In this review, we present the novel substrates and regulators of the PARP1-catalyzed poly (ADP-ribosyl)ation (PARylatison) that have been identified in the last 3 years. The overall aim is the presentation of protein interactions of potential therapeutic intervention for overcoming the resistance to PARPi.</p>