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

doi:10.1016/j.molcel.2012.05.026

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

59 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 language	English (US)
Pages (from-to)	61-75
Number of pages	15
Journal	Molecular Cell
Volume	47
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2012.05.026
State	Published - 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

Yan, Z, Guo, R, Paramasivam, M, Shen, W, Ling, C, Fox, D, Wang, Y, Oostra, AB, Kuehl, J, Lee, DY, Takata, M, Hoatlin, ME, Schindler, D, Joenje, H, de Winter, JP, Li, L, Seidman, MM & Wang, W 2012, 'A Ubiquitin-Binding Protein, FAAP20, Links RNF8-Mediated Ubiquitination to the Fanconi Anemia DNA Repair Network', Molecular Cell, vol. 47, no. 1, pp. 61-75. https://doi.org/10.1016/j.molcel.2012.05.026

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

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.",

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

note = "Funding Information: We thank Drs. D. Durocher, M. Huen, and A.R. Meetei for reagents, and Dr. David Schlessinger for critical reading of the manuscript. This work was supported in part by the Intramural Research Program of the National Institute on Aging (AG000688-07), National Institutes of Health. ",

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doi = "10.1016/j.molcel.2012.05.026",

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AU - Yan, Zhijiang

AU - Guo, Rong

AU - Paramasivam, Manikandan

AU - Shen, Weiping

AU - Ling, Chen

AU - Fox, David

AU - Wang, Yucai

AU - Oostra, Anneke B.

AU - Kuehl, Julia

AU - Lee, Duck Yeon

AU - Takata, Minoru

AU - Hoatlin, Maureen E.

AU - Schindler, Detlev

AU - Joenje, Hans

AU - de Winter, Johan P.

AU - Li, Lei

AU - Seidman, Michael M.

AU - Wang, Weidong

N1 - Funding Information: We thank Drs. D. Durocher, M. Huen, and A.R. Meetei for reagents, and Dr. David Schlessinger for critical reading of the manuscript. This work was supported in part by the Intramural Research Program of the National Institute on Aging (AG000688-07), National Institutes of Health.

PY - 2012/7/13

Y1 - 2012/7/13

N2 - 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.

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

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