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Science. 2010 Aug 6;329(5992):693-6. doi: 10.1126/science.1192656. Epub 2010 Jul 29.

FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.

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  • 1Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.

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.

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PMID:
20671156
[PubMed - indexed for MEDLINE]
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