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RAD51 recombinase
A filament of Rad51 based on PDB: 1SZP .[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols RAD51 ; BRCC5; FANCR; HRAD51; HsRad51; HsT16930; MRMV2; RAD51A; RECA
External IDs OMIM179617 MGI97890 HomoloGene2155 GeneCards: RAD51 Gene
RNA expression pattern
PBB GE RAD51 205024 s at tn.png
PBB GE RAD51 205023 at tn.png
More reference expression data
Species Human Mouse
Entrez 5888 19361
Ensembl ENSG00000051180 ENSMUSG00000027323
UniProt Q06609 Q08297
RefSeq (mRNA) NM_001164269 NM_011234
RefSeq (protein) NP_001157741 NP_035364
Location (UCSC) Chr 15:
40.69 – 40.73 Mb
Chr 2:
119.11 – 119.15 Mb
PubMed search [1] [2]

RAD51 is a eukaryote gene. The protein encoded by this gene is a member of the RAD51 protein family which assist in repair of DNA double strand breaks. RAD51 family members are homologous to the bacterial RecA, Archaeal RadA and yeast Rad51.[2] The protein is highly conserved in most eukaryotes, from yeast to humans.[3]


Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. Transcript variants utilizing alternative polyA signals exist.


In mammals, seven recA-like genes have been identified: Rad51, Rad51L1/B, Rad51L2/C, Rad51L3/D, XRCC2, XRCC3, and DMC1/Lim15.[4] All of these proteins, with the exception of meiosis-specific DMC1, are essential for development in mammals. Rad51 is a member of the RecA-like NTPases.


In humans, RAD51 is a 339-amino acid protein that plays a major role in homologous recombination of DNA during double strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a template strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process.

Unlike other proteins involved in DNA metabolism, the RecA/Rad51 family forms a helical nucleoprotein filament on DNA.[5]

This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2[6] and RAD52.

The structural basis for Rad51 filament formation and its functional mechanism still remain poorly understood. However, recent studies using fluorescent labeled Rad51[7] has indicated that Rad51 fragments elongate via multiple nucleation events followed by growth, with the total fragment terminating when it reaches about 2 μm in length. Disassociation of Rad51 from dsDNA, however, is slow and incomplete, suggesting that there is a separate mechanism that accomplishes this.


This protein is also found to interact with PALB2[6] and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.[8]

Several alterations of the Rad51 gene have been associated with an increased risk of developing breast cancer. The breast cancer susceptibility protein BRCA2 and PALB2 controls the function of Rad51 in the pathway for DNA repair by homologous recombination.[6][9] Increased RAD51 expression levels have been identified in metastatic canine mammary carcinoma, indicating that genomic instability plays an important role in the carcinogenesis of this tumor type.[10][11][12][13]


RAD51 has been shown to interact with:


  1. ^ Conway AB, Lynch TW, Zhang Y, Fortin GS, Fung CW, Symington LS, Rice PA. (2004). "Crystal structure of a Rad51 filament". Nat Struct Mol Biol 11 (8): 791–6. doi:10.1038/nsmb795. PMID 15235592. 
  2. ^ Shinohara A, Ogawa H, Ogawa T (May 1992). "Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein". Cell 69 (3): 457–70. doi:10.1016/0092-8674(92)90447-K. PMID 1581961. 
  3. ^ Shinohara A, Ogawa H, Matsuda Y, Ushio N, Ikeo K, Ogawa T (Jul 1993). "Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA". Nature Genetics 4 (3): 239–43. doi:10.1038/ng0793-239. PMID 8358431. 
  4. ^ Kawabata M, Kawabata T, Nishibori M (Feb 2005). "Role of recA/RAD51 family proteins in mammals". Acta Medica Okayama 59 (1): 1–9. PMID 15902993. 
  5. ^ Galkin VE, Wu Y, Zhang XP, Qian X, He Y, Yu X, Heyer WD, Luo Y, Egelman EH (Jun 2006). "The Rad51/RadA N-terminal domain activates nucleoprotein filament ATPase activity". Structure 14 (6): 983–92. doi:10.1016/j.str.2006.04.001. PMID 16765891. 
  6. ^ a b c Buisson R, Dion-Côté AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, Stasiak A, Xia B, Masson JY (Oct 2010). "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination". Nature Structural & Molecular Biology 17 (10): 1247–54. doi:10.1038/nsmb.1915. PMID 20871615. 
  7. ^ Hilario J, Amitani I, Baskin RJ, Kowalczykowski SC (Jan 2009). "Direct imaging of human Rad51 nucleoprotein dynamics on individual DNA molecules". Proceedings of the National Academy of Sciences of the United States of America 106 (2): 361–8. doi:10.1073/pnas.0811965106. PMC 2613362. PMID 19122145. 
  8. ^ Daniel DC (Oct 2002). "Highlight: BRCA1 and BRCA2 proteins in breast cancer". Microscopy Research and Technique 59 (1): 68–83. doi:10.1002/jemt.10178. PMID 12242698. 
  9. ^ a b Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, Venkitaraman AR (Nov 2002). "Insights into DNA recombination from the structure of a RAD51-BRCA2 complex". Nature 420 (6913): 287–93. doi:10.1038/nature01230. PMID 12442171. 
  10. ^ Klopfleisch R, von Euler H, Sarli G, Pinho SS, Gärtner F, Gruber AD (Jan 2011). "Molecular carcinogenesis of canine mammary tumors: news from an old disease". Veterinary Pathology 48 (1): 98–116. doi:10.1177/0300985810390826. PMID 21149845. 
  11. ^ Klopfleisch R, Gruber AD (May 2009). "Increased expression of BRCA2 and RAD51 in lymph node metastases of canine mammary adenocarcinomas". Veterinary Pathology 46 (3): 416–22. doi:10.1354/vp.08-VP-0212-K-FL. PMID 19176491. 
  12. ^ Klopfleisch R, Schütze M, Gruber AD (Jan 2010). "RAD51 protein expression is increased in canine mammary carcinomas". Veterinary Pathology 47 (1): 98–101. doi:10.1177/0300985809353310. PMID 20080488. 
  13. ^ Klopfleisch R, Klose P, Gruber AD (May 2010). "The combined expression pattern of BMP2, LTBP4, and DERL1 discriminates malignant from benign canine mammary tumors". Veterinary Pathology 47 (3): 446–54. doi:10.1177/0300985810363904. PMID 20375427. 
  14. ^ a b c Chen G, Yuan SS, Liu W, Xu Y, Trujillo K, Song B, Cong F, Goff SP, Wu Y, Arlinghaus R, Baltimore D, Gasser PJ, Park MS, Sung P, Lee EY (Apr 1999). "Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl". The Journal of Biological Chemistry 274 (18): 12748–52. PMID 10212258. 
  15. ^ a b c d e f Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R (Nov 2003). "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair". Molecular Cell 12 (5): 1087–99. PMID 14636569. 
  16. ^ a b Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R (Sep 1998). "Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells". Molecular Cell 2 (3): 317–28. PMID 9774970. 
  17. ^ Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM (Jan 1997). "Association of BRCA1 with Rad51 in mitotic and meiotic cells". Cell 88 (2): 265–75. PMID 9008167. 
  18. ^ Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene MI (Aug 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. PMID 11498787. 
  19. ^ Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C, Sands A, Eichele G, Hasty P, Bradley A (Apr 1997). "Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2". Nature 386 (6627): 804–10. doi:10.1038/386804a0. PMID 9126738. 
  20. ^ Lin HR, Ting NS, Qin J, Lee WH (Sep 2003). "M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the dissociation of the BRCA2-P/CAF complex". The Journal of Biological Chemistry 278 (38): 35979–87. doi:10.1074/jbc.M210659200. PMID 12815053. 
  21. ^ Yu DS, Sonoda E, Takeda S, Huang CL, Pellegrini L, Blundell TL, Venkitaraman AR (Oct 2003). "Dynamic control of Rad51 recombinase by self-association and interaction with BRCA2". Molecular Cell 12 (4): 1029–41. PMID 14580352. 
  22. ^ Chen PL, Chen CF, Chen Y, Xiao J, Sharp ZD, Lee WH (Apr 1998). "The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment". Proceedings of the National Academy of Sciences of the United States of America 95 (9): 5287–92. PMC 20253. PMID 9560268. 
  23. ^ Sarkisian CJ, Master SR, Huber LJ, Ha SI, Chodosh LA (Oct 2001). "Analysis of murine Brca2 reveals conservation of protein-protein interactions but differences in nuclear localization signals". The Journal of Biological Chemistry 276 (40): 37640–8. doi:10.1074/jbc.M106281200. PMID 11477095. 
  24. ^ Wong AK, Pero R, Ormonde PA, Tavtigian SV, Bartel PL (Dec 1997). "RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2". The Journal of Biological Chemistry 272 (51): 31941–4. PMID 9405383. 
  25. ^ Katagiri T, Saito H, Shinohara A, Ogawa H, Kamada N, Nakamura Y, Miki Y (Mar 1998). "Multiple possible sites of BRCA2 interacting with DNA repair protein RAD51". Genes, Chromosomes & Cancer 21 (3): 217–22. PMID 9523196. 
  26. ^ Tarsounas M, Davies AA, West SC (Jan 2004). "RAD51 localization and activation following DNA damage". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 359 (1441): 87–93. doi:10.1098/rstb.2003.1368. PMC 1693300. PMID 15065660. 
  27. ^ Liu J, Yuan Y, Huan J, Shen Z (Jan 2001). "Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2". Oncogene 20 (3): 336–45. doi:10.1038/sj.onc.1204098. PMID 11313963. 
  28. ^ Marmorstein LY, Ouchi T, Aaronson SA (Nov 1998). "The BRCA2 gene product functionally interacts with p53 and RAD51". Proceedings of the National Academy of Sciences of the United States of America 95 (23): 13869–74. PMC 24938. PMID 9811893. 
  29. ^ Wu L, Davies SL, Levitt NC, Hickson ID (Jun 2001). "Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51". The Journal of Biological Chemistry 276 (22): 19375–81. doi:10.1074/jbc.M009471200. PMID 11278509. 
  30. ^ Masson JY, Davies AA, Hajibagheri N, Van Dyck E, Benson FE, Stasiak AZ, Stasiak A, West SC (Nov 1999). "The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51". The EMBO Journal 18 (22): 6552–60. doi:10.1093/emboj/18.22.6552. PMC 1171718. PMID 10562567. 
  31. ^ Sigurdsson S, Van Komen S, Petukhova G, Sung P (Nov 2002). "Homologous DNA pairing by human recombination factors Rad51 and Rad54". The Journal of Biological Chemistry 277 (45): 42790–4. doi:10.1074/jbc.M208004200. PMID 12205100. 
  32. ^ Stürzbecher HW, Donzelmann B, Henning W, Knippschild U, Buchhop S (Apr 1996). "p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction". The EMBO Journal 15 (8): 1992–2002. PMC 450118. PMID 8617246. 
  33. ^ Buchhop S, Gibson MK, Wang XW, Wagner P, Stürzbecher HW, Harris CC (Oct 1997). "Interaction of p53 with the human Rad51 protein". Nucleic Acids Research 25 (19): 3868–74. PMC 146972. PMID 9380510. 
  34. ^ Tanaka K, Hiramoto T, Fukuda T, Miyagawa K (Aug 2000). "A novel human rad54 homologue, Rad54B, associates with Rad51". The Journal of Biological Chemistry 275 (34): 26316–21. doi:10.1074/jbc.M910306199. PMID 10851248. 
  35. ^ Kovalenko OV, Plug AW, Haaf T, Gonda DK, Ashley T, Ward DC, Radding CM, Golub EI (Apr 1996). "Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes". Proceedings of the National Academy of Sciences of the United States of America 93 (7): 2958–63. PMC 39742. PMID 8610150. 
  36. ^ Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (Oct 1996). "Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system". Genomics 37 (2): 183–6. doi:10.1006/geno.1996.0540. PMID 8921390. 

External links[edit]