Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1998 Mar 1;26(5):1179–1184. doi: 10.1093/nar/26.5.1179

Isolation and characterization of RAD51C, a new human member of the RAD51 family of related genes.

M K Dosanjh 1, D W Collins 1, W Fan 1, G G Lennon 1, J S Albala 1, Z Shen 1, D Schild 1
PMCID: PMC147393  PMID: 9469824

Abstract

The yeast and human RAD51 genes encode strand-transfer proteins that are thought to be involved in both recombinational repair of DNA damage and meiotic recombination. In yeast, the Rad51 family of related proteins also includes Rad55, Rad57 and Dmc1. In mammalian cells, five genes in this family have been identified (HsRAD51, XRCC2, XRCC3, RAD51B/hREC2 and HsDMC1), and here we report the isolation of the sixth member, RAD51C. RAD51C was originally identified by a computer screen of the EST database. A full-length approximately 1.3 kb cDNA clone has been isolated that encodes a protein of 376 aa, having a 18-26% aa identity with other human Rad51 family members. RAD51C includes a previously mapped sequenced-tagged site location near the end of chromosome 17q. The RAD51C transcript is expressed in various human tissues, with highest level of expression in testis, followed by heart muscle, spleen and prostate. Yeast two-hybrid experiments indicate that the Rad51C protein binds to two other members of the Rad51 protein family (Xrcc3 and Rad51B) but not to itself. These findings suggest that Rad51C may function similarly to the yeast Rad55 or Rad57 proteins, rather than as a Rad51 functional homolog.

Full Text

The Full Text of this article is available as a PDF (652.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aboussekhra A., Chanet R., Adjiri A., Fabre F. Semidominant suppressors of Srs2 helicase mutations of Saccharomyces cerevisiae map in the RAD51 gene, whose sequence predicts a protein with similarities to procaryotic RecA proteins. Mol Cell Biol. 1992 Jul;12(7):3224–3234. doi: 10.1128/mcb.12.7.3224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albala J. S., Thelen M. P., Prange C., Fan W., Christensen M., Thompson L. H., Lennon G. G. Identification of a novel human RAD51 homolog, RAD51B. Genomics. 1997 Dec 15;46(3):476–479. doi: 10.1006/geno.1997.5062. [DOI] [PubMed] [Google Scholar]
  3. Bartel P. L., Fields S. Analyzing protein-protein interactions using two-hybrid system. Methods Enzymol. 1995;254:241–263. doi: 10.1016/0076-6879(95)54018-0. [DOI] [PubMed] [Google Scholar]
  4. Baumann P., Benson F. E., West S. C. Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro. Cell. 1996 Nov 15;87(4):757–766. doi: 10.1016/s0092-8674(00)81394-x. [DOI] [PubMed] [Google Scholar]
  5. Campbell K. S., Buder A., Deuschle U. Interactions between the amino-terminal domain of p56lck and cytoplasmic domains of CD4 and CD8 alpha in yeast. Eur J Immunol. 1995 Aug;25(8):2408–2412. doi: 10.1002/eji.1830250842. [DOI] [PubMed] [Google Scholar]
  6. Clever B., Interthal H., Schmuckli-Maurer J., King J., Sigrist M., Heyer W. D. Recombinational repair in yeast: functional interactions between Rad51 and Rad54 proteins. EMBO J. 1997 May 1;16(9):2535–2544. doi: 10.1093/emboj/16.9.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Game J. C. DNA double-strand breaks and the RAD50-RAD57 genes in Saccharomyces. Semin Cancer Biol. 1993 Apr;4(2):73–83. [PubMed] [Google Scholar]
  8. Golub E. I., Kovalenko O. V., Gupta R. C., Ward D. C., Radding C. M. Interaction of human recombination proteins Rad51 and Rad54. Nucleic Acids Res. 1997 Oct 15;25(20):4106–4110. doi: 10.1093/nar/25.20.4106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Habu T., Taki T., West A., Nishimune Y., Morita T. The mouse and human homologs of DMC1, the yeast meiosis-specific homologous recombination gene, have a common unique form of exon-skipped transcript in meiosis. Nucleic Acids Res. 1996 Feb 1;24(3):470–477. doi: 10.1093/nar/24.3.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harper J. W., Adami G. R., Wei N., Keyomarsi K., Elledge S. J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. doi: 10.1016/0092-8674(93)90499-g. [DOI] [PubMed] [Google Scholar]
  11. Hays S. L., Firmenich A. A., Berg P. Complex formation in yeast double-strand break repair: participation of Rad51, Rad52, Rad55, and Rad57 proteins. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6925–6929. doi: 10.1073/pnas.92.15.6925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ivanov E. L., Haber J. E. DNA repair: RAD alert. Curr Biol. 1997 Aug 1;7(8):R492–R495. doi: 10.1016/s0960-9822(06)00246-6. [DOI] [PubMed] [Google Scholar]
  13. James P., Halladay J., Craig E. A. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics. 1996 Dec;144(4):1425–1436. doi: 10.1093/genetics/144.4.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jiang H., Xie Y., Houston P., Stemke-Hale K., Mortensen U. H., Rothstein R., Kodadek T. Direct association between the yeast Rad51 and Rad54 recombination proteins. J Biol Chem. 1996 Dec 27;271(52):33181–33186. doi: 10.1074/jbc.271.52.33181. [DOI] [PubMed] [Google Scholar]
  15. Johnson R. D., Symington L. S. Functional differences and interactions among the putative RecA homologs Rad51, Rad55, and Rad57. Mol Cell Biol. 1995 Sep;15(9):4843–4850. doi: 10.1128/mcb.15.9.4843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kovalenko O. V., Plug A. W., Haaf T., Gonda D. K., Ashley T., Ward D. C., Radding C. M., Golub E. I. Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2958–2963. doi: 10.1073/pnas.93.7.2958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kozak M. Interpreting cDNA sequences: some insights from studies on translation. Mamm Genome. 1996 Aug;7(8):563–574. doi: 10.1007/s003359900171. [DOI] [PubMed] [Google Scholar]
  18. Milne G. T., Weaver D. T. Dominant negative alleles of RAD52 reveal a DNA repair/recombination complex including Rad51 and Rad52. Genes Dev. 1993 Sep;7(9):1755–1765. doi: 10.1101/gad.7.9.1755. [DOI] [PubMed] [Google Scholar]
  19. Mizuta R., LaSalle J. M., Cheng H. L., Shinohara A., Ogawa H., Copeland N., Jenkins N. A., Lalande M., Alt F. W. RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51 protein. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6927–6932. doi: 10.1073/pnas.94.13.6927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morita T., Yoshimura Y., Yamamoto A., Murata K., Mori M., Yamamoto H., Matsushiro A. A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6577–6580. doi: 10.1073/pnas.90.14.6577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Peterson C., Legerski R. High-frequency transformation of human repair-deficient cell lines by an Epstein-Barr virus-based cDNA expression vector. Gene. 1991 Nov 15;107(2):279–284. doi: 10.1016/0378-1119(91)90328-9. [DOI] [PubMed] [Google Scholar]
  22. Rice M. C., Smith S. T., Bullrich F., Havre P., Kmiec E. B. Isolation of human and mouse genes based on homology to REC2, a recombinational repair gene from the fungus Ustilago maydis. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7417–7422. doi: 10.1073/pnas.94.14.7417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scully R., Chen J., Plug A., Xiao Y., Weaver D., Feunteun J., Ashley T., Livingston D. M. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell. 1997 Jan 24;88(2):265–275. doi: 10.1016/s0092-8674(00)81847-4. [DOI] [PubMed] [Google Scholar]
  24. Sharan S. K., Morimatsu M., Albrecht U., Lim D. S., Regel E., Dinh C., Sands A., Eichele G., Hasty P., Bradley A. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature. 1997 Apr 24;386(6627):804–810. doi: 10.1038/386804a0. [DOI] [PubMed] [Google Scholar]
  25. Shen Z., Cloud K. G., Chen D. J., Park M. S. Specific interactions between the human RAD51 and RAD52 proteins. J Biol Chem. 1996 Jan 5;271(1):148–152. doi: 10.1074/jbc.271.1.148. [DOI] [PubMed] [Google Scholar]
  26. Shen Z., Pardington-Purtymun P. E., Comeaux J. C., Moyzis R. K., Chen D. J. Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system. Genomics. 1996 Oct 15;37(2):183–186. doi: 10.1006/geno.1996.0540. [DOI] [PubMed] [Google Scholar]
  27. Shen Z., Pardington-Purtymun P. E., Comeaux J. C., Moyzis R. K., Chen D. J. UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins. Genomics. 1996 Sep 1;36(2):271–279. doi: 10.1006/geno.1996.0462. [DOI] [PubMed] [Google Scholar]
  28. Shinohara A., Ogawa H., Matsuda Y., Ushio N., Ikeo K., Ogawa T. Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA. Nat Genet. 1993 Jul;4(3):239–243. doi: 10.1038/ng0793-239. [DOI] [PubMed] [Google Scholar]
  29. Shinohara A., Ogawa H., Ogawa T. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell. 1992 May 1;69(3):457–470. doi: 10.1016/0092-8674(92)90447-k. [DOI] [PubMed] [Google Scholar]
  30. Stürzbecher H. W., Donzelmann B., Henning W., Knippschild U., Buchhop S. p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction. EMBO J. 1996 Apr 15;15(8):1992–2002. [PMC free article] [PubMed] [Google Scholar]
  31. Sung P., Robberson D. L. DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with polarity opposite to that of RecA. Cell. 1995 Aug 11;82(3):453–461. doi: 10.1016/0092-8674(95)90434-4. [DOI] [PubMed] [Google Scholar]
  32. Sung P. Yeast Rad55 and Rad57 proteins form a heterodimer that functions with replication protein A to promote DNA strand exchange by Rad51 recombinase. Genes Dev. 1997 May 1;11(9):1111–1121. doi: 10.1101/gad.11.9.1111. [DOI] [PubMed] [Google Scholar]
  33. Tebbs R. S., Zhao Y., Tucker J. D., Scheerer J. B., Siciliano M. J., Hwang M., Liu N., Legerski R. J., Thompson L. H. Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6354–6358. doi: 10.1073/pnas.92.14.6354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thompson L. H. Evidence that mammalian cells possess homologous recombinational repair pathways. Mutat Res. 1996 Jun 12;363(2):77–88. doi: 10.1016/0921-8777(96)00008-0. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES