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| | ==Solution Structure of ERCC4 domain of human FAAP24== | | ==Solution Structure of ERCC4 domain of human FAAP24== |
| - | <StructureSection load='2m9m' size='340' side='right' caption='[[2m9m]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2m9m' size='340' side='right'caption='[[2m9m]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m9m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M9M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M9M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m9m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M9M FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m9n|2m9n]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FAAP24, C19orf40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2m9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m9m OCA], [https://pdbe.org/2m9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m9m RCSB], [https://www.ebi.ac.uk/pdbsum/2m9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m9m ProSAT]</span></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=2m9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m9m OCA], [http://pdbe.org/2m9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m9m RCSB], [http://www.ebi.ac.uk/pdbsum/2m9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2m9m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FAP24_HUMAN FAP24_HUMAN]] Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA. | + | [https://www.uniprot.org/uniprot/FAP24_HUMAN FAP24_HUMAN] Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA. |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Gong, W]] | + | [[Category: Large Structures]] |
| - | [[Category: Han, X]] | + | [[Category: Gong W]] |
| - | [[Category: Shi, C]] | + | [[Category: Han X]] |
| - | [[Category: Tian, C]] | + | [[Category: Shi C]] |
| - | [[Category: Wu, F]] | + | [[Category: Tian C]] |
| - | [[Category: Dna binding protein]]
| + | [[Category: Wu F]] |
| - | [[Category: Ercc4 domain]]
| + | |
| - | [[Category: Faap24]]
| + | |
| - | [[Category: Fanconi anemia]]
| + | |
| Structural highlights
Function
FAP24_HUMAN Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA.
Publication Abstract from PubMed
The FANCM/FAAP24 heterodimer has distinct functions in protecting cells from complex DNA lesions such as interstrand crosslinks. These functions rely on the biochemical activity of FANCM/FAAP24 to recognize and bind to damaged DNA or stalled replication forks. However, the DNA-binding activity of this complex was not clearly defined. We investigated how FAAP24 contributes to the DNA-interacting functions of the FANCM/FAAP24 complex by acquiring the N-terminal and C-terminal solution structures of human FAAP24. Modeling of the FAAP24 structure indicates that FAAP24 may possess a high affinity toward single-stranded DNA (ssDNA). Testing of various FAAP24 mutations in vitro and in vivo validated this prediction derived from structural analyses. We found that the DNA-binding and FANCM-interacting functions of FAAP24, although both require the C-terminal (HhH)2 domain, can be distinguished by segregation-of-function mutations. These results demonstrate dual roles of FAAP24 in DNA damage response against crosslinking lesions, one through the formation of FANCM/FAAP24 heterodimer and the other via its ssDNA-binding activity required in optimized checkpoint activation.Cell Research advance online publication 3 September 2013; doi:10.1038/cr.2013.124.
Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response.,Wang Y, Han X, Wu F, Leung JW, Lowery MG, Do H, Chen J, Shi C, Tian C, Li L, Gong W Cell Res. 2013 Sep 3. doi: 10.1038/cr.2013.124. PMID:23999858[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang Y, Han X, Wu F, Leung JW, Lowery MG, Do H, Chen J, Shi C, Tian C, Li L, Gong W. Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response. Cell Res. 2013 Sep 3. doi: 10.1038/cr.2013.124. PMID:23999858 doi:10.1038/cr.2013.124
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