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Poly(ADP-Ribose) Polymerases 1 and 2: Classical Functions and Interaction with New Histone Poly(ADP-Ribosyl)ation Factor HPF1

  • CELL MOLECULAR BIOLOGY: FROM DNA REPAIR TO METABOLOMICS
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Abstract

Poly(ADP-ribose) (PAR) is a negatively charged polymer, linear or branched, that consists of ADP-ribose monomers. PAR is synthesized by poly(ADP-ribose)polymerase (PARP) enzymes, which are activated upon DNA damage and use nicotinamide adenine dinucleotide (NAD+) as a substrate. The best-studied members of the PARP family, PARP1 and PARP2, are the most important nuclear proteins involved in many cell processes, including the regulation of DNA repair. PARP1 and PARP2 catalyze PAR synthesis and transfer to amino acid residues of target proteins, including autoPARylation. PARP1 and PARP2 are promising targets for chemotherapy in view of their key role in regulating DNA repair. A novel histone PARylation factor (HPF1) was recently discovered to modulate PARP1/2 activity by forming a transient joint active site with PARP1/2. Histones are modified at serine residues in the presence of HPF1. The general mechanism of the interaction between HPF1 and PARP1/2 is a subject of intense research now. The review considers the discovery and classical mechanism of PARylation in higher eukaryotes and the role of HPF1 in the process.

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ACKNOWLEDGMENTS

We are grateful to N.I. Rechkunova for fruitful discussion of the review.

Funding

This work was supported by the Russian Science Foundation (project no. 22-14-00112) and a state contract with the Institute of Chemical Biology and Fundamental Medicine (no. 121031300041-4, part “Several Aspects of the Roles of PARP1 and PARP2 in the Cell”).

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  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    T. A. Kurgina & O. I. Lavrik

  2. Novosibirsk State University, 630090, Novosibirsk, Russia

    O. I. Lavrik

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  1. T. A. Kurgina
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Correspondence to O. I. Lavrik.

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Translated by T. Tkacheva

Abbreviations: ARH3, ADP-ribosylhydrolase 3; ART, ADP-ribosyltransferase; BER, base excision repair; HDAC, histone deacetylase; HPF1, histone PARylation factor 1; MAR, mono(ADP-ribose); MARylation, mono(ADP-ribosyl)ation; MSK1/2, mitogen- and stress-activated protein kinase 1/2; PARP1/2, poly(ADP-ribose)polymerase 1/2; PARG, poly(ADP-ribose)glycohydrolase; Polβ, DNA polymerase β; PAR, poly(ADP-ribose); PARylation, poly(ADP-rybosyl)ation; XRCC1, X-ray repair cross-complementing protein 1.

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Kurgina, T.A., Lavrik, O.I. Poly(ADP-Ribose) Polymerases 1 and 2: Classical Functions and Interaction with New Histone Poly(ADP-Ribosyl)ation Factor HPF1. Mol Biol 57, 245–257 (2023). https://doi.org/10.1134/S0026893323020140

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