| 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]
Publication Abstract from PubMed
The central step in eukaryotic homologous recombination (HR) is ATP-dependent DNA-strand exchange mediated by the Rad51 recombinase. In this process, Rad51 assembles on single-stranded DNA (ssDNA) and generates a helical filament that is able to search for and invade homologous double-stranded DNA (dsDNA), thus leading to strand separation and formation of new base pairs between the initiating ssDNA and the complementary strand within the duplex. Here, we used cryo-EM to solve the structures of human RAD51 in complex with DNA molecules, in presynaptic and postsynaptic states, at near-atomic resolution. Our structures reveal both conserved and distinct structural features of the human RAD51-DNA complexes compared with their prokaryotic counterpart. Notably, we also captured the structure of an arrested synaptic complex. Our results provide new insight into the molecular mechanisms of the DNA homology search and strand-exchange processes.
Cryo-EM structures of human RAD51 recombinase filaments during catalysis of DNA-strand exchange.,Xu J, Zhao L, Xu Y, Zhao W, Sung P, Wang HW Nat Struct Mol Biol. 2017 Jan;24(1):40-46. doi: 10.1038/nsmb.3336. Epub 2016 Dec , 12. PMID:27941862[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Xu J, Zhao L, Xu Y, Zhao W, Sung P, Wang HW. Cryo-EM structures of human RAD51 recombinase filaments during catalysis of DNA-strand exchange. Nat Struct Mol Biol. 2017 Jan;24(1):40-46. doi: 10.1038/nsmb.3336. Epub 2016 Dec , 12. PMID:27941862 doi:http://dx.doi.org/10.1038/nsmb.3336
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