@article{793ac139ac704f4c82eba3f341e42005,
title = "ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures",
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.",
keywords = "Biological Sciences, Cell Biology, Molecular Biology",
author = "Shibo Li and Hongyan Lu and Zi Wang and Qing Hu and Hongjun Wang and Rong Xiang and Takuya Chiba and Xiaohua Wu",
note = "Funding Information: We thank Dr. Orlando D. Sch{\"a}rer for valuable suggestions and comments on this work. The HCT116 FANCM KO cell line was kindly provided by Dr. Lei Li (University of Texas MD Anderson Cancer Center). XPF-WT cDNA was kindly provided by Dr. Stephen C. West (The Francis Crick Institute, UK). The shRNA vector pLKO.1-blast (#26655)and gRNA/Cas9 vector pSpCas9(BB)-2A-Puro (PX459)V2.0 (Addgene #62988)are from Addgene. This work is supported by NIH grants CA187052, CA197995, and GM080677 to X.W. Conceptualization, X.W. and S.L.; Investigation, S.L. H.L. Z.W. Q.H. and H.W.; Writing – Original Draft, X.W. and S.L.; Writing – Review & Editing, X.W. S.L. H.L. and Z.W. Supervision, X.W. R.X. and T.C.; Funding Acquisition: X.W. The authors declare no competing interests. Funding Information: This work is supported by NIH grants CA187052 , CA197995 , and GM080677 to X.W. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = jun,
day = "28",
doi = "10.1016/j.isci.2019.05.017",
language = "English",
volume = "16",
pages = "63--78",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
}