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 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

doi:10.1016/j.molcel.2012.05.026

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. Epub 2012 Jun 14.

Authors

Zhijiang Yan¹, 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

Affiliation

¹ Laboratory of Genetics, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224, USA.

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.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Amino Acid Sequence
Animals
Cell Line, Tumor
DNA Repair*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Fanconi Anemia / genetics
Fanconi Anemia / metabolism
Fanconi Anemia Complementation Group D2 Protein / genetics
Fanconi Anemia Complementation Group D2 Protein / metabolism*
Fanconi Anemia Complementation Group Proteins / chemistry
Fanconi Anemia Complementation Group Proteins / genetics
Fanconi Anemia Complementation Group Proteins / metabolism*
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
HEK293 Cells
HeLa Cells
Humans
Immunoblotting
Lysine / chemistry
Lysine / genetics
Lysine / metabolism
Microscopy, Fluorescence
Molecular Sequence Data
Mutation
Protein Binding
Protein Structure, Tertiary
RNA Interference
Sequence Homology, Amino Acid
Signal Transduction
Ubiquitin / metabolism
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism
Ubiquitination*

Substances

DNA-Binding Proteins
FAAP20 protein, human
Fanconi Anemia Complementation Group D2 Protein
Fanconi Anemia Complementation Group Proteins
RNF8 protein, human
Ubiquitin
Green Fluorescent Proteins
Ubiquitin-Protein Ligases
Lysine

Abstract

Publication types

MeSH terms

Substances

Grants and funding