ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures

Shibo Li, Hongyan Lu, Zi Wang, Qing Hu, Hongjun Wang, Rong Xiang, Takuya Chiba, Xiaohua Wu

Research output: Contribution to journalArticle

Abstract

The structure-specific endonuclease ERCC1/XPF plays an important role in nucleotide excision repair and interstrand cross-link repair. In this study, we identified new functions of ERCC1/XPF in DNA double-strand break (DSB)repair. We found that the conserved function of ERCC1/XPF to remove non-homologous sequences at DSBs is a rate-limiting step for homologous recombination in mammalian cells, and more importantly, we uncovered an indispensable role of ERCC1/XPF in repair of DSBs containing DNA secondary structures, including the structure-prone AT-rich DNA sequences derived from common fragile sites and G-quadruplexes (G4s). We also demonstrated a synthetic lethal interaction of XPF with DNA translocase FANCM that is involved in removing DNA secondary structures. Furthermore, inactivation of XPF sensitizes FANCM-deficient cells to G4-interacting compounds. These results suggest an important function of ERCC1/XPF in protecting DNA secondary structures and provide a rationale for targeted treatment of FANCM-deficient tumors through inhibition of XPF.

Original languageEnglish
Pages (from-to)63-78
Number of pages16
JournalFood Science and Human Wellness
Volume16
DOIs
Publication statusPublished - 2019 Jun 28

Fingerprint

Double-Stranded DNA Breaks
DNA repair
DNA
AT Rich Sequence
G-Quadruplexes
Endonucleases
Homologous Recombination
DNA Repair
homologous recombination
lethal genes
inactivation
cells
nucleotide sequences
neoplasms
Neoplasms
1,2-di-(4-sulfamidophenyl)-4-butylpyrazolidine-3,5-dione

Keywords

  • Biological Sciences
  • Cell Biology
  • Molecular Biology

ASJC Scopus subject areas

  • Food Science
  • General

Cite this

ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures. / Li, Shibo; Lu, Hongyan; Wang, Zi; Hu, Qing; Wang, Hongjun; Xiang, Rong; Chiba, Takuya; Wu, Xiaohua.

In: Food Science and Human Wellness, Vol. 16, 28.06.2019, p. 63-78.

Research output: Contribution to journalArticle

Li, Shibo ; Lu, Hongyan ; Wang, Zi ; Hu, Qing ; Wang, Hongjun ; Xiang, Rong ; Chiba, Takuya ; Wu, Xiaohua. / ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures. In: Food Science and Human Wellness. 2019 ; Vol. 16. pp. 63-78.
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AU - Xiang, Rong

AU - Chiba, Takuya

AU - Wu, Xiaohua

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