8gbj

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8gbj]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GBJ FirstGlance]. <br>
<table><tr><td colspan='2'>[[8gbj]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GBJ FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.11&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></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=8gbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gbj OCA], [https://pdbe.org/8gbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gbj RCSB], [https://www.ebi.ac.uk/pdbsum/8gbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gbj 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=8gbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gbj OCA], [https://pdbe.org/8gbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gbj RCSB], [https://www.ebi.ac.uk/pdbsum/8gbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gbj ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[https://www.uniprot.org/uniprot/RA51C_HUMAN RA51C_HUMAN] Fanconi anemia;Hereditary breast and ovarian cancer syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
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[https://www.uniprot.org/uniprot/RA51D_HUMAN RA51D_HUMAN] Hereditary breast and/or ovarian cancer syndrome;Familial prostate cancer. Disease susceptibility is associated with variants affecting the gene represented in this entry.
== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/RA51C_HUMAN RA51C_HUMAN] Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD51 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis.<ref>PMID:14716019</ref> <ref>PMID:16215984</ref> <ref>PMID:16395335</ref> <ref>PMID:19451272</ref> <ref>PMID:19783859</ref> <ref>PMID:20413593</ref> <ref>PMID:23108668</ref> <ref>PMID:23149936</ref>
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[https://www.uniprot.org/uniprot/RA51D_HUMAN RA51D_HUMAN] Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Bind to single-stranded DNA (ssDNA) and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. Involved in telomere maintenance. The BCDX2 subcomplex XRCC2:RAD51D can stimulate Holliday junction resolution by BLM.<ref>PMID:10871607</ref> <ref>PMID:11751635</ref> <ref>PMID:11834724</ref> <ref>PMID:11842113</ref> <ref>PMID:12975363</ref> <ref>PMID:15109494</ref> <ref>PMID:23149936</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Homologous recombination (HR) fulfils a pivotal role in the repair of DNA double-strand breaks and collapsed replication forks(1). HR depends on the products of several paralogues of RAD51, including the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 (BCDX2)(2). BCDX2 functions as a mediator of nucleoprotein filament assembly by RAD51 and single-stranded DNA (ssDNA) during HR, but its mechanism remains undefined. Here we report cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis yields insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Moreover, our cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer(3-6) inactivate DNA binding and the HR mediator activity of BCDX2. Our findings shed light on the role of BCDX2 in HR and provide a foundation for understanding how pathogenic alterations in BCDX2 impact genome repair.
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Structural insights into BCDX2 complex function in homologous recombination.,Rawal Y, Jia L, Meir A, Zhou S, Kaur H, Ruben EA, Kwon Y, Bernstein KA, Jasin M, Taylor AB, Burma S, Hromas R, Mazin AV, Zhao W, Zhou D, Wasmuth EV, Greene EC, Sung P, Olsen SK Nature. 2023 Jul;619(7970):640-649. doi: 10.1038/s41586-023-06219-w. Epub 2023 , Jun 21. PMID:37344589<ref>PMID:37344589</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8gbj" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Current revision

Cryo-EM structure of a human BCDX2/ssDNA complex

PDB ID 8gbj

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