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Poly(ADP-ribose) polymerase enzymes and the maintenance of genome integrity

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Abstract

DNA damage response (DDR) relies on swift and accurate signaling to rapidly identify DNA lesions and initiate repair. A critical DDR signaling and regulatory molecule is the posttranslational modification poly(ADP-ribose) (PAR). PAR is synthesized by a family of structurally and functionally diverse proteins called poly(ADP-ribose) polymerases (PARPs). Although PARPs share a conserved catalytic domain, unique regulatory domains of individual family members endow PARPs with unique properties and cellular functions. Family members PARP-1, PARP-2, and PARP-3 (DDR–PARPs) are catalytically activated in the presence of damaged DNA and act as damage sensors. Family members tankyrase-1 and closely related tankyrase-2 possess SAM and ankyrin repeat domains that regulate their diverse cellular functions. Recent studies have shown that the tankyrases share some overlapping functions with the DDR–PARPs, and even perform novel functions that help preserve genomic integrity. In this review, we briefly touch on DDR–PARP functions, and focus on the emerging roles of tankyrases in genome maintenance. Preservation of genomic integrity thus appears to be a common function of several PARP family members, depicting PAR as a multifaceted guardian of the genome.

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Acknowledgements

Pascal laboratory research on PARP enzymes is supported by grants from the Canadian Institute of Health Research (BMA342854 and PJT374609).

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  1. Travis Eisemann

    Present address: Department of Molecular Biology, Princeton University, Princeton, NJ, USA

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  1. Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA

    Travis Eisemann

  2. Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, Canada

    John M. Pascal

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Eisemann, T., Pascal, J.M. Poly(ADP-ribose) polymerase enzymes and the maintenance of genome integrity. Cell. Mol. Life Sci. 77, 19–33 (2020). https://doi.org/10.1007/s00018-019-03366-0

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