@article{18719c179ff0439abf8f503fe88c8cee,
title = "RPA activates the XPF-ERCC1 endonuclease to initiate processing of DNA interstrand crosslinks",
abstract = "During replication-coupled DNA interstrand crosslink (ICL) repair, the XPF-ERCC1 endonuclease is required for the incisions that release, or “unhook”, ICLs, but the mechanism of ICL unhooking remains largely unknown. Incisions are triggered when the nascent leading strand of a replication fork strikes the ICL. Here, we report that while purified XPF-ERCC1 incises simple ICL-containing model replication fork structures, the presence of a nascent leading strand, modelling the effects of replication arrest, inhibits this activity. Strikingly, the addition of the single-stranded DNA (ssDNA)-binding replication protein A (RPA) selectively restores XPF-ERCC1 endonuclease activity on this structure. The 5′–3′ exonuclease SNM1A can load from the XPF-ERCC1-RPA-induced incisions and digest past the crosslink to quantitatively complete the unhooking reaction. We postulate that these collaborative activities of XPF-ERCC1, RPA and SNM1A might explain how ICL unhooking is achieved in vivo.",
author = "Abdullah, {Ummi B} and McGouran, {Joanna F} and Sanja Brolih and Denis Ptchelkine and El‐Sagheer, {Afaf H} and Tom Brown and McHugh, {Peter J}",
note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: We thank our laboratory member Sook Y. Lee and Opher Gileadi (Structural Genomics Consortium, Oxford) for the recombinant SNM1A; Fumiko Esashi (Dunn School of Pathology, University of Oxford) and Marc Wold (Iowa State University, USA) for the RPA and RPA70ΔC442, respectively; Hannah Baddock (WIMM), Hazel Aitkenhead and Joseph A. Newman (Structural Genomics Consortium, University of Oxford) for assistance with fluorescence anisotropy. P.J.M. was supported by MRC (Medical Research Council, grant MR/L007665/1). A.H.E.S. and T.B. were supported by BBSRC (Biotechnology and Biological Sciences Research Council, grant BB/J001694/1) BBSRC: sLOLA grant BB/J001694/1 “Extending the boundaries of nucleic acid chemistry” J.F.M. was supported by King Abdullah University of Science and Technology (KAUST) for a grant awarded to B. Nord{\'e}n. U.B.A. was supported by the Malaysia's King Scholarship (Biasiswa Yang Di-Pertuan Agong). This publication acknowledges KAUST support, but has no KAUST affiliated authors.",
year = "2017",
month = jun,
day = "12",
doi = "10.15252/embj.201796664",
language = "English (US)",
volume = "36",
pages = "2047--2060",
journal = "The EMBO Journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "14",
}