西亚试剂：FAN1 Acts with FANCI-FANCD2 to Promote DNA Interstrand Cros

FAN1 Acts with FANCI-FANCD2 to Promote DNA Interstrand Cross-Link Repair
Ting Liu,1,* Gargi Ghosal,2,* Jingsong Yuan,2 Junjie Chen,2, Jun Huang1,

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 monoubiquitylation 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 monoubiquitylation of the ID complex. Thus, the monoubiquitylated 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.

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