SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair.
XRCC1 is an essential scaffold protein for base excision repair (BER) and helps to maintain genomic stability. XRCC1 has been indicated as a substrate for small ubiquitin-like modifier modification (SUMOylation); however, how XRCC1 SUMOylation is regulated in cells and how SUMOylated XRCC1 regulates BER activity are not well understood. Here, ... we show that SUMOylation of XRCC1 is regulated in cells under methyl-methanesulfonate (MMS) treatment and facilitates BER. Poly(ADP-ribose) polymerase 1 (PARP1) is activated by MMS immediately and synthesizes poly(ADP-ribose) (PAR), which in turn promotes recruitment of SUMO E3 TOPORS to XRCC1 and facilitates XRCC1 SUMOylation. A SUMOylation-defective mutant of XRCC1 had lower binding activity for DNA polymerase beta (POLB) and was linked to a lower capacity for repair of MMS-induced DNA damages. Our study therefore identified a pathway in which DNA damage-induced poly(ADP-ribosyl)ation (PARylation) promotes SUMOylation of XRCC1, which leads to more efficient recruitment of POLB to complete BER.
Mesh Terms:
Alcohol Oxidoreductases, DNA Damage, DNA Polymerase beta, DNA Repair, DNA-Binding Proteins, Genomic Instability, Humans, Methyl Methanesulfonate, Poly (ADP-Ribose) Polymerase-1, Poly ADP Ribosylation, Protein Binding, Sumoylation, X-ray Repair Cross Complementing Protein 1
Alcohol Oxidoreductases, DNA Damage, DNA Polymerase beta, DNA Repair, DNA-Binding Proteins, Genomic Instability, Humans, Methyl Methanesulfonate, Poly (ADP-Ribose) Polymerase-1, Poly ADP Ribosylation, Protein Binding, Sumoylation, X-ray Repair Cross Complementing Protein 1
Hum. Mol. Genet.
Date: Dec. 01, 2017
PubMed ID: 29668892
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