ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures
Summary: 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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-06-01
|
| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219301543 |
| _version_ | 1818589895178846208 |
|---|---|
| author | Shibo Li Hongyan Lu Zi Wang Qing Hu Hongjun Wang Rong Xiang Takuya Chiba Xiaohua Wu |
| author_facet | Shibo Li Hongyan Lu Zi Wang Qing Hu Hongjun Wang Rong Xiang Takuya Chiba Xiaohua Wu |
| author_sort | Shibo Li |
| collection | DOAJ |
| description | Summary: 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. : Biological Sciences; Molecular Biology; Cell Biology Subject Areas: Biological Sciences, Molecular Biology, Cell Biology |
| first_indexed | 2024-12-16T09:47:55Z |
| format | Article |
| id | doaj.art-d06af5111e1347beabeb54e18a22b4e4 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T09:47:55Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d06af5111e1347beabeb54e18a22b4e42022-12-21T22:36:07ZengElsevieriScience2589-00422019-06-01166378ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary StructuresShibo Li0Hongyan Lu1Zi Wang2Qing Hu3Hongjun Wang4Rong Xiang5Takuya Chiba6Xiaohua Wu7Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, ChinaDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Biomedical Gerontology Laboratory, Department of Health Science and Social Welfare, School of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa 359-1192, JapanDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USASchool of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, ChinaBiomedical Gerontology Laboratory, Department of Health Science and Social Welfare, School of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa 359-1192, JapanDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Corresponding authorSummary: 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. : Biological Sciences; Molecular Biology; Cell Biology Subject Areas: Biological Sciences, Molecular Biology, Cell Biologyhttp://www.sciencedirect.com/science/article/pii/S2589004219301543 |
| spellingShingle | Shibo Li Hongyan Lu Zi Wang Qing Hu Hongjun Wang Rong Xiang Takuya Chiba Xiaohua Wu ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures iScience |
| title | ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures |
| title_full | ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures |
| title_fullStr | ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures |
| title_full_unstemmed | ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures |
| title_short | ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures |
| title_sort | ercc1 xpf is important for repair of dna double strand breaks containing secondary structures |
| url | http://www.sciencedirect.com/science/article/pii/S2589004219301543 |
| work_keys_str_mv | AT shiboli ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures AT hongyanlu ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures AT ziwang ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures AT qinghu ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures AT hongjunwang ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures AT rongxiang ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures AT takuyachiba ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures AT xiaohuawu ercc1xpfisimportantforrepairofdnadoublestrandbreakscontainingsecondarystructures |