2. Academic Validation
  3. A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network

A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network

  • Mol Cell. 2012 Jul 13;47(1):61-75. doi: 10.1016/j.molcel.2012.05.026.
Zhijiang Yan 1,  Rong Guo,  Manikandan Paramasivam,  Weiping Shen,  Chen Ling,  David Fox 3rd,  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
Affiliations

Affiliation

  • 1 Laboratory of Genetics, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224, USA.
PMID: 22705371 DOI: 10.1016/j.molcel.2012.05.026
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.

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