@article{1a502c0fafbf46bf9bb3cac7d98f7951,
title = "RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair",
abstract = "SLX4/FANCP is a key Fanconi anemia (FA) protein and a DNA repair scaffold for incision around a DNA interstrand crosslink (ICL) by its partner XPF nuclease. The tandem UBZ4 ubiquitin-binding domains of SLX4 are critical for the recruitment of SLX4 to damage sites, likely by binding to K63-linked polyubiquitin chains. However, the identity of the ubiquitin E3 ligase that mediates SLX4 recruitment remains unknown. Using small interfering RNA (siRNA) screening with a GFP-tagged N-terminal half of SLX4 (termed SLX4-N), we identify the RNF168 E3 ligase as a critical factor for mitomycin C (MMC)-induced SLX4 foci formation. RNF168 and GFP-SLX4-N colocalize in MMC-induced ubiquitin foci. Accumulation of SLX4-N at psoralen-laser ICL tracks or of endogenous SLX4 at Digoxigenin-psoralen/UVA ICL is dependent on RNF168. Finally, we find that RNF168 is epistatic with SLX4 in promoting MMC tolerance. We conclude that RNF168 is a critical component of the signal transduction that recruits SLX4 to ICL damage.",
author = "Yoko Katsuki and Masako Abe and Park, {Seon Young} and Wenwen Wu and Hiromasa Yabe and Miharu Yabe and {van Attikum}, Haico and Shinichiro Nakada and Tomohiko Ohta and Seidman, {Michael M.} and Yonghwan Kim and Minoru Takata",
note = "Funding Information: The authors would like to thank Professor James Hejna for critical reading of the manuscript and English editing; Drs. Masatoshi Fujita, Kazumasa Yoshida, Bunsho Shiotani, Atsushi Shibata, Andres Canela, and Anfeng Mu for discussions and help; Ms. Masami Tanaka and Kumi Johchi for technical and secretarial assistance; Dr. David L. Spector for U2OS 2-6-3 cells carrying the LacO array; Drs. John Rouse, Hiroyuki Miyoshi, Makoto Nakanishi, Masato Kanemaki, and Feng Zhang for plasmids; Drs. Fuyuki Ishikawa and Tomoichiro Miyoshi for anti-TRF2 antibody; Drs. Hiroshi Harada and Minoru Kobayashi for FACSCantoII; and Dr. Takayuki Yamashita for GM6914. This work was supported by grants from JSPS (KAKENHI grant numbers JP23114010 , JP15H01738 , and JP20H03450 to M.T. and JP17K12822 and JP20K12161 to Y. Katsuki), the European Research Council (ERC Consolidator 617485 , H.v.A.), the Dutch Research Council (NWO VICI VI.C.182.052 , H.v.A.), the Uehara Memorial Foundation (M.T.), Astellas Foundation for Research on Metabolic Disorders (M.T.), Kyoto University Research Funds (Core Stage Back-Up to M.T.), Future Development Funding Program of Kyoto University Research Coordination Alliance (Y. Katsuki), Kyoto University Foundation (Y. Katsuki), and National Research Foundation of Korea (MSIP, 2019R1A2C2089746 to Y. Kim). This work is also supported by the JSPS Core-to-Core Program (grant number JPJSCCA20200009 ). The Radiation Biology Center, Graduate School of Biostudies, Kyoto University is a joint usage research center certified by the MEXT, Japan. Funding Information: The authors would like to thank Professor James Hejna for critical reading of the manuscript and English editing; Drs. Masatoshi Fujita, Kazumasa Yoshida, Bunsho Shiotani, Atsushi Shibata, Andres Canela, and Anfeng Mu for discussions and help; Ms. Masami Tanaka and Kumi Johchi for technical and secretarial assistance; Dr. David L. Spector for U2OS 2-6-3 cells carrying the LacO array; Drs. John Rouse, Hiroyuki Miyoshi, Makoto Nakanishi, Masato Kanemaki, and Feng Zhang for plasmids; Drs. Fuyuki Ishikawa and Tomoichiro Miyoshi for anti-TRF2 antibody; Drs. Hiroshi Harada and Minoru Kobayashi for FACSCantoII; and Dr. Takayuki Yamashita for GM6914. This work was supported by grants from JSPS (KAKENHI grant numbers JP23114010, JP15H01738, and JP20H03450 to M.T. and JP17K12822 and JP20K12161 to Y. Katsuki), the European Research Council (ERC Consolidator 617485, H.v.A.), the Dutch Research Council (NWO VICI VI.C.182.052, H.v.A.), the Uehara Memorial Foundation (M.T.), Astellas Foundation for Research on Metabolic Disorders (M.T.), Kyoto University Research Funds (Core Stage Back-Up to M.T.), Future Development Funding Program of Kyoto University Research Coordination Alliance (Y. Katsuki), Kyoto University Foundation (Y. Katsuki), and National Research Foundation of Korea (MSIP, 2019R1A2C2089746 to Y. Kim). This work is also supported by the JSPS Core-to-Core Program (grant number JPJSCCA20200009). The Radiation Biology Center, Graduate School of Biostudies, Kyoto University is a joint usage research center certified by the MEXT, Japan. M.T. and Y. Katsuki planned the study with consultation with S.N. and Y. Kim. Y. Katsuki carried out most of the experiments with help from M.A. in automated cytometry, H.v.A. in RNF168 chromatin tethering, W.W. and T.O. in TMP-UV laser experiments, and M.M.S in Dig-TMP/UVA experiments. H.Y. and M.Y. initiated culture of TKFA-45 fibroblasts that was transformed by S.Y.P. and Y. Kim. M.T. Y. Katsuki, M.M.S. and Y. Kim analyzed the data. M.T. and Y. Katsuki wrote the paper. The authors declare there are no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = oct,
day = "26",
doi = "10.1016/j.celrep.2021.109879",
language = "English",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}