Serine ADP-ribosylation in DNA-damage response regulation

PARP1 and PARP2 govern the DNA-damage response by catalysing the reversible post-translational modification ADPribosylation. During the repair of DNA lesions, PARP1 and PARP2 combine with an accessory factor HPF1, which is required for the modification of target proteins on serine residues. Although the physiological role of individual ADPribosylation sites is still unclear, serine ADP-ribosylation at damage sites leads to the recruitment of chromatin remodellers and repair factors to ensure efficient DNA repair. ADPribosylation signalling is tightly controlled by the coordinated activities of (ADP-ribosyl)glycohydrolases PARG and ARH3 that, by reversing the modification, guarantee proper kinetics of DNA repair and cell cycle re-entry. The recent advances in the structural and mechanistic understanding of ADP-ribosylation provide new insights into human physiopathology and cancer therapy.

Automated summary

PARP1 and PARP2 regulate DNA damage response by catalyzing reversible post-translational modification ADPribosylation. Serine ADP-ribosylation at damage sites leads to recruitment of repair factors for efficient DNA repair. Tight control of ADPribosylation signaling by (ADP-ribosyl)glycohydrolases ensures proper kinetics of DNA repair and cell cycle re-entry, providing new insights into human physiopathology and cancer therapy.