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4ri9

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FAN1 Nuclease bound to 5' phosphorylated p(dT)/3'(dT-dT-dT-dT-dT-dT-dT-dT) double flap DNA

Structural highlights

4ri9 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FAN1_HUMAN Karyomegalic interstitial nephritis. The disease is caused by mutations affecting the gene represented in this entry.

Function

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.^[1] ^[2] ^[3] ^[4]

References

↑ MacKay C, Declais AC, Lundin C, Agostinho A, Deans AJ, MacArtney TJ, Hofmann K, Gartner A, West SC, Helleday T, Lilley DM, Rouse J. Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2. Cell. 2010 Jul 9;142(1):65-76. doi: 10.1016/j.cell.2010.06.021. PMID:20603015 doi:http://dx.doi.org/10.1016/j.cell.2010.06.021
↑ Kratz K, Schopf B, Kaden S, Sendoel A, Eberhard R, Lademann C, Cannavo E, Sartori AA, Hengartner MO, Jiricny J. Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell. 2010 Jul 9;142(1):77-88. doi: 10.1016/j.cell.2010.06.022. PMID:20603016 doi:http://dx.doi.org/10.1016/j.cell.2010.06.022
↑ Smogorzewska A, Desetty R, Saito TT, Schlabach M, Lach FP, Sowa ME, Clark AB, Kunkel TA, Harper JW, Colaiacovo MP, Elledge SJ. A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair. Mol Cell. 2010 Jul 9;39(1):36-47. doi: 10.1016/j.molcel.2010.06.023. PMID:20603073 doi:http://dx.doi.org/10.1016/j.molcel.2010.06.023
↑ Liu T, Ghosal G, Yuan J, Chen J, Huang J. FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair. Science. 2010 Aug 6;329(5992):693-6. doi: 10.1126/science.1192656. Epub 2010 Jul , 29. PMID:20671156 doi:http://dx.doi.org/10.1126/science.1192656