PolyADP-ribosylation

PolyADP-ribosylation, also known as parylation, is the post-translational modification process by which polymers of ADP-ribose (poly(adenosinediphosphate-ribose)) are covalently attached to proteins by PAR polymerase enzymes. The polymerase covalently attaches poly(ADP-ribose) polymer to itself and appropriate acceptors such as histones and other DNA-associated proteins. Parylation regulates chromatin organization, DNA repair, transcription and replication and other processes.

Latest Research and Reviews

  • Research
    | Open Access

    HPF1 controls the ADP-ribosylation activity of PARP1/2 in response to DNA breaks. Here, the authors show that HPF1 regulates the balance between ADP-ribose initiation and elongation through a dynamic interaction that accelerates the initiation rate on serine residues.

    • Marie-France Langelier
    • , Ramya Billur
    •  & John M. Pascal
  • Research
    | Open Access

    SPINDOC is known to interact with Spindlin1 (SPIN1), a histone code effector protein. Here, the authors show that SPINDOC is distributed between two distinct protein complexes, one comprising SPIN1 and the other one with PARP1. Their results suggest a role for SPINDOC in the regulation of PARP1- mediated PARylation and the DNA damage response.

    • Fen Yang
    • , Jianji Chen
    •  & Mark T. Bedford
  • Research
    | Open Access

    ADP-ribosylation is regulated by HPF1 and ARH3, but the cellular target spectrum of these enzymes is not fully understood. Here, the authors use quantitative proteomics to define the HPF1- and ARH3-dependent ADP-ribosylome, providing evidence that mono-ADP-ribosylation of serine predominates in cells.

    • Ivo A. Hendriks
    • , Sara C. Buch-Larsen
    •  & Michael L. Nielsen
  • Research
    | Open Access

    PARG and ARH3 are the main hydrolases to reverse serine poly(ADP-ribosylation) yet their activities in the process differ. Here, the authors synthesise linear and branched poly(ADP-ribose) molecules, perform structure-function analysis and elucidate the mechanistic differences between PARG and ARH3.

    • Johannes Gregor Matthias Rack
    • , Qiang Liu
    •  & Ivan Ahel
  • Research
    | Open Access

    PARP inhibitors function by trapping PARP1 protein on DNA breaks, which has cytotoxic consequences to cancer cells. Here the authors identify three serine residues within PARP1 as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance.

    • Evgeniia Prokhorova
    • , Florian Zobel
    •  & Ivan Ahel
  • Research
    | Open Access

    Poly(ADP-ribose) polymerase 2 (PARP2) is activated by 5′-phosphorylated DNA breaks but the molecular mechanism is not fully understood. Here, the authors report a crystal structure of PARP2 bound to an activating DNA fragment, providing insights into the structural changes that lead to PARP2 activation.

    • Ezeogo Obaji
    • , Mirko M. Maksimainen
    •  & Lari Lehtiö

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