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

研究成果: 雜誌貢獻文章

摘要

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.
原文英語
頁(從 - 到)2306-2317
頁數12
期刊Human Molecular Genetics
27
發行號13
DOIs
出版狀態已發佈 - 七月 1 2018

指紋

Sumoylation
DNA Repair
Adenosine Diphosphate
Methyl Methanesulfonate
DNA Damage
DNA Polymerase beta
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Genomic Instability
Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

引用此文

Hu, L. Y., Chang, C. C., Huang, Y. S., Chou, W. C., Lin, Y. M., Ho, C. C., ... 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

SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair. / Hu, Ling Yueh; Chang, Che Chang; Huang, Yen Sung; Chou, Wen Cheng; Lin, Ying Mei; Ho, Chun Chen; Chen, Wei Ting; Shih, Hsiu Ming; Hsiung, Chia Ni; Wu, Pei Ei; Shen, Chen Yang.

於: Human Molecular Genetics, 卷 27, 編號 13, 01.07.2018, p. 2306-2317.

研究成果: 雜誌貢獻文章

Hu, LY, Chang, CC, Huang, YS, Chou, WC, Lin, YM, Ho, CC, Chen, WT, Shih, HM, Hsiung, CN, Wu, PE & Shen, CY 2018, 'SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair', Human Molecular Genetics, 卷 27, 編號 13, 頁 2306-2317. https://doi.org/10.1093/hmg/ddy135
Hu, Ling Yueh ; Chang, Che Chang ; Huang, Yen Sung ; Chou, Wen Cheng ; Lin, Ying Mei ; Ho, Chun Chen ; Chen, Wei Ting ; Shih, Hsiu Ming ; Hsiung, Chia Ni ; Wu, Pei Ei ; Shen, Chen Yang. / SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair. 於: Human Molecular Genetics. 2018 ; 卷 27, 編號 13. 頁 2306-2317.
@article{de630a92e902445186d27d03114972a3,
title = "SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair",
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.",
author = "Hu, {Ling Yueh} and Chang, {Che Chang} and Huang, {Yen Sung} and Chou, {Wen Cheng} and Lin, {Ying Mei} and Ho, {Chun Chen} and Chen, {Wei Ting} and Shih, {Hsiu Ming} and Hsiung, {Chia Ni} and Wu, {Pei Ei} and Shen, {Chen Yang}",
year = "2018",
month = "7",
day = "1",
doi = "10.1093/hmg/ddy135",
language = "English",
volume = "27",
pages = "2306--2317",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "13",

}

TY - JOUR

T1 - SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair

AU - Hu, Ling Yueh

AU - Chang, Che Chang

AU - Huang, Yen Sung

AU - Chou, Wen Cheng

AU - Lin, Ying Mei

AU - Ho, Chun Chen

AU - Chen, Wei Ting

AU - Shih, Hsiu Ming

AU - Hsiung, Chia Ni

AU - Wu, Pei Ei

AU - Shen, Chen Yang

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85050809329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050809329&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddy135

DO - 10.1093/hmg/ddy135

M3 - Article

VL - 27

SP - 2306

EP - 2317

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 13

ER -