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

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

doi:10.3389/fphar.2023.1137151

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

Front Pharmacol. 2023 Feb 23:14:1137151. doi: 10.3389/fphar.2023.1137151. eCollection 2023.

Authors

Tao Zhu¹, Ju-Yan Zheng², Ling-Ling Huang¹, Yan-Hong Wang¹, Di-Fei Yao¹, Hai-Bin Dai¹

Affiliations

¹ Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.

Abstract

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⁺, 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 BRCA1/2-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.

Keywords: DNA damage repair; PARP inhibitors; poly-ADP ribosylation; substrate; synthetic lethality.

Publication types

Review

Grants and funding

This work was supported by the National Natural Science Foundation of China (82204517) and Science and Technology Program in Medicine and Health of Zhejiang Province (2023KY726).