4rec
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/FAN1_HUMAN FAN1_HUMAN]] Nuclease required for maintenance of chromosomal stability. Plays a key role in DNA repair of DNA interstrand cross-links (ICL) by being recruited to sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL-induced DNA breaks by being required for efficient homologous recombination, possibly in the resolution of homologous recombination intermediates. Not involved in DNA double-strand breaks resection. Has both endonuclease activity toward 5'-flaps and 5'-exonuclease activity: may act in concert with the 3'-flap-specific enzymes to unhook the ICL by cleaving the lagging-strand template.<ref>PMID:20603015</ref> <ref>PMID:20603016</ref> <ref>PMID:20603073</ref> <ref>PMID:20671156</ref> | [[http://www.uniprot.org/uniprot/FAN1_HUMAN FAN1_HUMAN]] Nuclease required for maintenance of chromosomal stability. Plays a key role in DNA repair of DNA interstrand cross-links (ICL) by being recruited to sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL-induced DNA breaks by being required for efficient homologous recombination, possibly in the resolution of homologous recombination intermediates. Not involved in DNA double-strand breaks resection. Has both endonuclease activity toward 5'-flaps and 5'-exonuclease activity: may act in concert with the 3'-flap-specific enzymes to unhook the ICL by cleaving the lagging-strand template.<ref>PMID:20603015</ref> <ref>PMID:20603016</ref> <ref>PMID:20603073</ref> <ref>PMID:20671156</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5' flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA and unwind a 5' flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1. | ||
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| + | Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer.,Zhao Q, Xue X, Longerich S, Sung P, Xiong Y Nat Commun. 2014 Dec 11;5:5726. doi: 10.1038/ncomms6726. PMID:25500724<ref>PMID:25500724</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 07:32, 14 January 2015
A nuclease-DNA complex form 3
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Categories: Longerich, S | Sung, P | Xiong, Y | Xue, X | Zhao, Q | Fancid2 | Hjc | Hydrolase-dna complex | Nucleus | Sap | Structure specific nuclease | Tpr
