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| | ==Structure of the FANCI-FANCD2 complex== | | ==Structure of the FANCI-FANCD2 complex== |
| - | <StructureSection load='3s4w' size='340' side='right' caption='[[3s4w]], [[Resolution|resolution]] 3.41Å' scene=''> | + | <StructureSection load='3s4w' size='340' side='right'caption='[[3s4w]], [[Resolution|resolution]] 3.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3s4w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S4W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S4W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3s4w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S4W FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3s51|3s51]], [[3s4z|3s4z]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3s51|3s51]], [[3s4z|3s4z]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fanci ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Fancd2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fanci ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Fancd2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3s4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s4w OCA], [http://pdbe.org/3s4w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s4w RCSB], [http://www.ebi.ac.uk/pdbsum/3s4w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s4w ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3s4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s4w OCA], [https://pdbe.org/3s4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s4w RCSB], [https://www.ebi.ac.uk/pdbsum/3s4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s4w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FANCI_MOUSE FANCI_MOUSE]] Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage. [[http://www.uniprot.org/uniprot/FACD2_MOUSE FACD2_MOUSE]] Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (By similarity). Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. | + | [[https://www.uniprot.org/uniprot/FANCI_MOUSE FANCI_MOUSE]] Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage. [[https://www.uniprot.org/uniprot/FACD2_MOUSE FACD2_MOUSE]] Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (By similarity). Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Pavletich, N P]] | | [[Category: Pavletich, N P]] |
| | [[Category: Dna binding protein]] | | [[Category: Dna binding protein]] |
| | [[Category: Dna repair]] | | [[Category: Dna repair]] |
| Structural highlights
Function
[FANCI_MOUSE] Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage. [FACD2_MOUSE] Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (By similarity). Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching.
Publication Abstract from PubMed
Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the ~300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each protein has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.
Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway.,Joo W, Xu G, Persky NS, Smogorzewska A, Rudge DG, Buzovetsky O, Elledge SJ, Pavletich NP Science. 2011 Jul 15;333(6040):312-6. PMID:21764741[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Joo W, Xu G, Persky NS, Smogorzewska A, Rudge DG, Buzovetsky O, Elledge SJ, Pavletich NP. Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway. Science. 2011 Jul 15;333(6040):312-6. PMID:21764741 doi:10.1126/science.1205805
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