A Ubiquitin-Binding Protein, FAAP20, Links RNF8-Mediated Ubiquitination to the Fanconi Anemia DNA Repair Network

Zhijiang Yan, Rong Guo, Manikandan Paramasivam, Weiping Shen, Chen Ling, David Fox, Yucai Wang, Anneke B. Oostra, Julia Kuehl, Duck Yeon Lee, Minoru Takata, Maureen E. Hoatlin, Detlev Schindler, Hans Joenje, Johan P. de Winter, Lei Li, Michael M. Seidman, Weidong Wang

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The Fanconi anemia (FA) protein network is necessary for repair of DNA interstrand crosslinks (ICLs), but its control mechanism remains unclear. Here we show that the network is regulated by a ubiquitin signaling cascade initiated by RNF8 and its partner, UBC13, and mediated by FAAP20, a component of the FA core complex. FAAP20 preferentially binds the ubiquitin product of RNF8-UBC13, and this ubiquitin-binding activity and RNF8-UBC13 are both required for recruitment of FAAP20 to ICLs. Both RNF8 and FAAP20 are required for recruitment of FA core complex and FANCD2 to ICLs, whereas RNF168 can modulate efficiency of the recruitment. RNF8 and FAAP20 are needed for efficient FANCD2 monoubiquitination, a key step of the FA network; RNF8 and the FA core complex work in the same pathway to promote cellular resistance to ICLs. Thus, the RNF8-FAAP20 ubiquitin cascade is critical for recruiting FA core complex to ICLs and for normal function of the FA network.

Original languageEnglish (US)
Pages (from-to)61-75
Number of pages15
JournalMolecular Cell
Volume47
Issue number1
DOIs
StatePublished - Jul 13 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Yan, Z., Guo, R., Paramasivam, M., Shen, W., Ling, C., Fox, D., Wang, Y., Oostra, A. B., Kuehl, J., Lee, D. Y., Takata, M., Hoatlin, M. E., Schindler, D., Joenje, H., de Winter, J. P., Li, L., Seidman, M. M., & Wang, W. (2012). A Ubiquitin-Binding Protein, FAAP20, Links RNF8-Mediated Ubiquitination to the Fanconi Anemia DNA Repair Network. Molecular Cell, 47(1), 61-75. https://doi.org/10.1016/j.molcel.2012.05.026