SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair

Ling Yueh Hu, Che Chang Chang, Yen Sung Huang, Wen Cheng Chou, Ying Mei Lin, Chun Chen Ho, Wei Ting Chen, Hsiu Ming Shih, Chia Ni Hsiung, Pei Ei Wu, Chen Yang Shen

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Abstract

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(ADPribose) 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 MMSinduced 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.

Original languageEnglish
Pages (from-to)2306-2317
Number of pages12
JournalHuman Molecular Genetics
Volume27
Issue number13
DOIs
Publication statusPublished - Jul 1 2018

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Hu, L. Y., Chang, C. C., Huang, Y. S., Chou, W. C., Lin, Y. M., Ho, C. C., Chen, W. T., Shih, H. M., Hsiung, C. N., Wu, P. E., & Shen, C. Y. (2018). SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair. Human Molecular Genetics, 27(13), 2306-2317. https://doi.org/10.1093/hmg/ddy135