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| | <StructureSection load='1n0w' size='340' side='right'caption='[[1n0w]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='1n0w' size='340' side='right'caption='[[1n0w]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1n0w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ ] and [https://en.wikipedia.org/wiki/Human Human]. The April 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''RecA and Rad51'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_4 10.2210/rcsb_pdb/mom_2014_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N0W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1n0w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''RecA and Rad51'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_4 10.2210/rcsb_pdb/mom_2014_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N0W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAD51 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BRCA2 ([https://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=1n0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n0w OCA], [https://pdbe.org/1n0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n0w RCSB], [https://www.ebi.ac.uk/pdbsum/1n0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n0w 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=1n0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n0w OCA], [https://pdbe.org/1n0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n0w RCSB], [https://www.ebi.ac.uk/pdbsum/1n0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n0w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN]] Defects in RAD51 are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:10807537</ref> Defects in RAD51 are the cause of mirror movements type 2 (MRMV2) [MIM:[https://omim.org/entry/614508 614508]]. A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.<ref>PMID:22305526</ref> [[https://www.uniprot.org/uniprot/BRCA2_HUMAN BRCA2_HUMAN]] Defects in BRCA2 are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:16793542</ref> <ref>PMID:8640237</ref> <ref>PMID:9150152</ref> <ref>PMID:9654203</ref> <ref>PMID:9609997</ref> <ref>PMID:9971877</ref> <ref>PMID:10399947</ref> <ref>PMID:10978364</ref> <ref>PMID:11139248</ref> <ref>PMID:11241844</ref> <ref>PMID:12145750</ref> <ref>PMID:12373604</ref> <ref>PMID:12442274</ref> <ref>PMID:12442275</ref> <ref>PMID:11948477</ref> <ref>PMID:12938098</ref> <ref>PMID:15026808</ref> <ref>PMID:15172753</ref> <ref>PMID:14722926</ref> <ref>PMID:15365993</ref> Defects in BRCA2 are the cause of pancreatic cancer type 2 (PNCA2) [MIM:[https://omim.org/entry/613347 613347]]. It is a malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.<ref>PMID:9140390</ref> Defects in BRCA2 are a cause of susceptibility to familial breast-ovarian cancer type 2 (BROVCA2) [MIM:[https://omim.org/entry/612555 612555]]. A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Defects in BRCA2 are the cause of Fanconi anemia complementation group D type 1 (FANCD1) [MIM:[https://omim.org/entry/605724 605724]]. It is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.<ref>PMID:12065746</ref> <ref>PMID:14670928</ref> <ref>PMID:16825431</ref> Defects in BRCA2 are a cause of glioma type 3 (GLM3) [MIM:[https://omim.org/entry/613029 613029]]. Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.<ref>PMID:15689453</ref>
| + | [https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN] Defects in RAD51 are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:10807537</ref> Defects in RAD51 are the cause of mirror movements type 2 (MRMV2) [MIM:[https://omim.org/entry/614508 614508]. A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.<ref>PMID:22305526</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN]] Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3.<ref>PMID:18417535</ref> <ref>PMID:12205100</ref> <ref>PMID:20413593</ref> [[https://www.uniprot.org/uniprot/BRCA2_HUMAN BRCA2_HUMAN]] Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. In concert with NPM1, regulates centrosome duplication.<ref>PMID:15115758</ref> <ref>PMID:15199141</ref> <ref>PMID:15671039</ref> <ref>PMID:18317453</ref> <ref>PMID:20729859</ref> <ref>PMID:20729858</ref> <ref>PMID:20729832</ref> <ref>PMID:21084279</ref>
| + | [https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN] Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3.<ref>PMID:18417535</ref> <ref>PMID:12205100</ref> <ref>PMID:20413593</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1n0w ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1n0w ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| - | <div style="background-color:#fffaf0;"> | |
| - | == Publication Abstract from PubMed == | |
| - | The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an evolutionarily conserved sequence in BRCA2 (the BRC repeat) and the RecA-homology domain of RAD51. The BRC repeat mimics a motif in RAD51 that serves as an interface for oligomerization between individual RAD51 monomers, thus enabling BRCA2 to control the assembly of the RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. The RAD51 oligomerization motif is highly conserved among RecA-like recombinases, highlighting a common evolutionary origin for the mechanism of nucleoprotein filament formation, mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC repeat disrupt its predicted interaction with RAD51, yielding structural insight into mechanisms for cancer susceptibility. | |
| - | | |
| - | Insights into DNA recombination from the structure of a RAD51-BRCA2 complex.,Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, Venkitaraman AR Nature. 2002 Nov 21;420(6913):287-93. Epub 2002 Nov 10. PMID:12442171<ref>PMID:12442171</ref> | |
| - | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | </div> | |
| - | <div class="pdbe-citations 1n0w" style="background-color:#fffaf0;"></div> | |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| | [[Category: RecA and Rad51]] | | [[Category: RecA and Rad51]] |
| - | [[Category: Anand, S]] | + | [[Category: Anand S]] |
| - | [[Category: Blundell, T L]] | + | [[Category: Blundell TL]] |
| - | [[Category: Lee, M]] | + | [[Category: Lee M]] |
| - | [[Category: Lo, T]] | + | [[Category: Lo T]] |
| - | [[Category: Pellegrini, L]] | + | [[Category: Pellegrini L]] |
| - | [[Category: Venkitaraman, A R]] | + | [[Category: Venkitaraman AR]] |
| - | [[Category: Yu, D S]] | + | [[Category: Yu DS]] |
| - | [[Category: Breast cancer susceptibility]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Gene regulation-antitumor protein complex]]
| + | |
| - | [[Category: Homologous recombination]]
| + | |
| - | [[Category: Protein complex]]
| + | |
| - | [[Category: Reca-like atpase]]
| + | |
| Structural highlights
Disease
RAD51_HUMAN Defects in RAD51 are a cause of susceptibility to breast cancer (BC) [MIM:114480. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.[1] Defects in RAD51 are the cause of mirror movements type 2 (MRMV2) [MIM:614508. A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.[2]
Function
RAD51_HUMAN Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3.[3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Kato M, Yano K, Matsuo F, Saito H, Katagiri T, Kurumizaka H, Yoshimoto M, Kasumi F, Akiyama F, Sakamoto G, Nagawa H, Nakamura Y, Miki Y. Identification of Rad51 alteration in patients with bilateral breast cancer. J Hum Genet. 2000;45(3):133-7. PMID:10807537 doi:10.1007/s100380050199
- ↑ Depienne C, Bouteiller D, Meneret A, Billot S, Groppa S, Klebe S, Charbonnier-Beaupel F, Corvol JC, Saraiva JP, Brueggemann N, Bhatia K, Cincotta M, Brochard V, Flamand-Roze C, Carpentier W, Meunier S, Marie Y, Gaussen M, Stevanin G, Wehrle R, Vidailhet M, Klein C, Dusart I, Brice A, Roze E. RAD51 haploinsufficiency causes congenital mirror movements in humans. Am J Hum Genet. 2012 Feb 10;90(2):301-7. doi: 10.1016/j.ajhg.2011.12.002. Epub, 2012 Feb 2. PMID:22305526 doi:10.1016/j.ajhg.2011.12.002
- ↑ Park JY, Yoo HW, Kim BR, Park R, Choi SY, Kim Y. Identification of a novel human Rad51 variant that promotes DNA strand exchange. Nucleic Acids Res. 2008 Jun;36(10):3226-34. doi: 10.1093/nar/gkn171. Epub 2008, Apr 16. PMID:18417535 doi:10.1093/nar/gkn171
- ↑ Sigurdsson S, Van Komen S, Petukhova G, Sung P. Homologous DNA pairing by human recombination factors Rad51 and Rad54. J Biol Chem. 2002 Nov 8;277(45):42790-4. Epub 2002 Aug 29. PMID:12205100 doi:10.1074/jbc.M208004200
- ↑ Sage JM, Gildemeister OS, Knight KL. Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome. J Biol Chem. 2010 Jun 18;285(25):18984-90. doi: 10.1074/jbc.M109.099846. Epub, 2010 Apr 22. PMID:20413593 doi:10.1074/jbc.M109.099846
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