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The Role of the WGR Domain in the Functions of PARP1 and PARP2

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Abstract

The PARP1 and PARP2 proteins are members of the poly(ADP-ribose) polymerase family involved in the regulation of DNA repair and replication, RNA processing, ribosome biogenesis, transcription, cell division, and cell death. PARP1 and PARP2 are promising targets for the development of anticancer drugs and can be used in the treatment of cardiovascular, neurodegenerative, and other disorders. The WGR domain has been shown to play a central role in the functioning of PARP1 and PARP2 proteins. This review considers the mechanisms of functioning of WGR domains in the PARP1 and PARP2 proteins, which have several similar and specialized properties. Understanding these processes is of great interest to fundamental science and can contribute to the development of more effective and selective inhibitors of PARP1 and PARP2.

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Funding

The work was supported by the Ministry of Science and Higher Education of the Russian Federation under Agreement no. 075-15-2021-1354 on October 7, 2021.

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Authors and Affiliations

  1. Department of Biology, Moscow State University, 119234, Moscow, Russia

    N. V. Maluchenko, A. N. Korovina, A. A. Saulina, V. M. Studitsky & A. V. Feofanov

  2. Fox Chase Cancer Center, PA 19111-2497, Philadelphia, United States

    V. M. Studitsky

  3. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    A. V. Feofanov

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  1. N. V. Maluchenko
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  2. A. N. Korovina
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  3. A. A. Saulina
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  5. A. V. Feofanov
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Correspondence to N. V. Maluchenko.

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Translated by A. Levina

Abbreviations: ART, ADP-ribozyltransferase domain; BRCT (BRCA1 C terminus), PARP1 domain that contains C-terminal motif, BRCA1 (breast cancer 1); CAT, catalytic domain; CTR, C-terminal region; FRAP, fluorescence recovery after photobleaching; HD, helical domain; HPF1, histone PARylation factor 1; NTR, N-terminal region; PAR, poly(ADP-ribose); PARP1, poly(ADP-ribose) polymerase 1; PARP2, poly(ADP-ribose) polymerase 2; SSBs and DSBs, single-strand breaks, double-strand breaks; WGR, tryptophan-glycine-arginine-rich domain (Trp (W), Gly (G), and Arg (R)); XRCC1 (X-ray repair cross-complementing 1), protein1 from complementation group, repair factor; Zn1, Zn2, and Zn3, zinc fingers 1, 2, and 3.

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Maluchenko, N.V., Korovina, A.N., Saulina, A.A. et al. The Role of the WGR Domain in the Functions of PARP1 and PARP2. Mol Biol 57, 802–810 (2023). https://doi.org/10.1134/S0026893323050114

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