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Science 329 (5992): 693-696

Copyright © 2010 by the American Association for the Advancement of Science

FAN1 Acts with FANCI-FANCD2 to Promote DNA Interstrand Cross-Link Repair

Ting Liu,1,* Gargi Ghosal,2,* Jingsong Yuan,2 Junjie Chen,2,{dagger} Jun Huang1,{dagger}

Abstract: Fanconi anemia (FA) is caused by mutations in 13 Fanc genes and renders cells hypersensitive to DNA interstrand cross-linking (ICL) agents. A central event in the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex. Here, we characterize a previously unrecognized nuclease, Fanconi anemia–associated nuclease 1 (FAN1), that promotes ICL repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex. Thus, the mono-ubiquitylated ID complex recruits the downstream repair protein FAN1 and facilitates the repair of DNA interstrand cross-links.

1 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
2 Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: jchen8{at}mdanderson.org (J.C.), jhuang{at}zju.edu.cn (J.H.)

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