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The function and regulation of ADP-ribosylation in the DNA damage response.

Lena DumaIvan Ahel
Published in: Biochemical Society transactions (2023)
ADP-ribosylation is a post-translational modification involved in DNA damage response (DDR). In higher organisms it is synthesised by PARP 1-3, DNA strand break sensors. Recent advances have identified serine residues as the most common targets for ADP-ribosylation during DDR. To ADP-ribosylate serine, PARPs require an accessory factor, HPF1 which completes the catalytic domain. Through ADP-ribosylation, PARPs recruit a variety of factors to the break site and control their activities. However, the timely removal of ADP-ribosylation is also key for genome stability and is mostly performed by two hydrolases: PARG and ARH3. Here, we describe the key writers, readers and erasers of ADP-ribosylation and their contribution to the mounting of the DDR. We also discuss the use of PARP inhibitors in cancer therapy and the ways to tackle PARPi treatment resistance.
Keyphrases
  • dna damage response
  • dna repair
  • cancer therapy
  • dna damage
  • drug delivery
  • protein kinase
  • dna methylation
  • circulating tumor
  • single molecule
  • oxidative stress
  • nucleic acid