The consequences of Rad51 overexpression for normal and tumor cells

DNA Repair

Volumn 7, Issue 5, 2008, Pages 686-693

  Klein, Hannah L ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Gene targeting; Genomic instability; Homologous recombination; Overexpression of Rad51; Rad51 protein; Tumor cell drug resistance

Indexed keywords

DOUBLE STRANDED DNA; HELICASE; PROTEIN P53; RAD51 PROTEIN; SINGLE STRANDED DNA;

APOPTOSIS; CANCER RESISTANCE; CARCINOGENESIS; CELL CYCLE; CELL DEATH; CELL TYPE; DNA BINDING; DNA DAMAGE; DNA REPAIR; DOUBLE STRANDED DNA BREAK; GENE DISRUPTION; GENE MUTATION; GENE OVEREXPRESSION; GENOMIC INSTABILITY; HOMOLOGOUS RECOMBINATION; HUMAN; INTERMEDIATE FILAMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TUMOR CELL;

ANIMALS; DROSOPHILA MELANOGASTER; GENE EXPRESSION; HUMANS; NEOPLASMS; RAD51 RECOMBINASE; RECOMBINATION, GENETIC; SACCHAROMYCES CEREVISIAE; SCHIZOSACCHAROMYCES;

EID: 42249115685     PISSN: 15687864     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.dnarep.2007.12.008     Document Type: Review

References (61)

1. Sung P., and Klein H. Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat. Rev. Mol. Cell. Biol. 7 (2006) 739-750
2. Baumann P., and West S.C. Role of the human RAD51 protein in homologous recombination and double-stranded-break repair. Trends Biochem. Sci. 23 (1998) 247-251
3. Krogh B.O., and Symington L.S. Recombination proteins in yeast. Annu. Rev. Genet. 38 (2004) 233-271
4. Symington L.S. Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol. Mol. Biol. Rev. 66 (2002) 630-670 table of contents
5. Lim D.S., and Hasty P. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Mol. Cell. Biol. 16 (1996) 7133-7143
6. Sonoda E., Sasaki M.S., Buerstedde J.M., Bezzubova O., Shinohara A., Ogawa H., Takata M., Yamaguchi-Iwai Y., and Takeda S. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J. 17 (1998) 598-608
7. Tsuzuki T., Fujii Y., Sakumi K., Tominaga Y., Nakao K., Sekiguchi M., Matsushiro A., Yoshimura Y., and Morita T. Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 6236-6240
8. Kim W.J., Lee H., Park E.J., Park J.K., and Park S.D. Gain- and loss-of-function of Rhp51, a Rad51 homolog in fission yeast, reveals dissimilarities in chromosome integrity. Nucleic Acids Res. 29 (2001) 1724-1732
9. Morgan E.A., Shah N., and Symington L.S. The requirement for ATP hydrolysis by Saccharomyces cerevisiae Rad51 is bypassed by mating-type heterozygosity or RAD54 in high copy. Mol. Cell. Biol. 22 (2002) 6336-6343
10. Sung P., and Stratton S.A. Yeast Rad51 recombinase mediates polar DNA strand exchange in the absence of ATP hydrolysis. J. Biol. Chem. 271 (1996) 27983-27986
11. 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. 11 (1997) 1111-1121
12. Sung P. Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J. Biol. Chem. 272 (1997) 28194-28197
13. Sung P., Krejci L., Van Komen S., and Sehorn M.G. Rad51 recombinase and recombination mediators. J. Biol. Chem. 278 (2003) 42729-42732
14. Asleson E.N., Okagaki R.J., and Livingston D.M. A core activity associated with the N terminus of the yeast RAD52 protein is revealed by RAD51 overexpression suppression of C-terminal rad52 truncation alleles. Genetics 153 (1999) 681-692
15. Milne G.T., Ho T., and Weaver D.T. Modulation of Saccharomyces cerevisiae DNA double-strand break repair by SRS2 and RAD51. Genetics 139 (1995) 1189-1199
16. Milne G.T., and Weaver D.T. Dominant negative alleles of RAD52 reveal a DNA repair/recombination complex including Rad51 and Rad52. Genes Dev. 7 (1993) 1755-1765
17. Schild D. Suppression of a new allele of the yeast RAD52 gene by overexpression of RAD51, mutations in srs2 and ccr4, or mating-type heterozygosity. Genetics 140 (1995) 115-127
18. Hays S.L., Firmenich A.A., and 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. 92 (1995) 6925-6929
19. Tsubouchi H., and Roeder G.S. The importance of genetic recombination for fidelity of chromosome pairing in meiosis. Dev. Cell 5 (2003) 915-925
20. Paffett K.S., Clikeman J.A., Palmer S., and Nickoloff J.A. Overexpression of Rad51 inhibits double-strand break-induced homologous recombination but does not affect gene conversion tract lengths. DNA Repair (Amst) 4 (2005) 687-698
21. Akaboshi E., Inoue Y., and Ryo H. Cloning of the cDNA and genomic DNA that correspond to the recA-like gene of Drosophila melanogaster. Jpn. J. Genet. 69 (1994) 663-670
22. McKee B.D., Ren X., and Hong C. A recA-like gene in Drosophila melanogaster that is expressed at high levels in female but not male meiotic tissues. Chromosoma 104 (1996) 479-488
23. Staeva-Vieira E., Yoo S., and Lehmann R. An essential role of DmRad51/SpnA in DNA repair and meiotic checkpoint control. EMBO J. 22 (2003) 5863-5874
24. Yoo S., and McKee B.D. Overexpression of Drosophila Rad51 protein (DmRad51) disrupts cell cycle progression and leads to apoptosis. Chromosoma 113 (2004) 92-101
25. Slupianek A., Schmutte C., Tombline G., Nieborowska-Skorska M., Hoser G., Nowicki M.O., Pierce A.J., Fishel R., and Skorski T. BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance. Mol. Cell 8 (2001) 795-806
26. Saintigny Y., Dumay A., Lambert S., and Lopez B.S. A novel role for the Bcl-2 protein family: specific suppression of the RAD51 recombination pathway. EMBO J. 20 (2001) 2596-2607
27. Pauklin S., Kristjuhan A., Maimets T., and Jaks V. ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress. Biochem. Biophys. Res. Commun. 334 (2005) 386-394
28. Arias-Lopez C., Lazaro-Trueba I., Kerr P., Lord C.J., Dexter T., Iravani M., Ashworth A., and Silva A. p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene. EMBO Rep. 7 (2006) 219-224
29. Hannay J.A., Liu J., Zhu Q.S., Bolshakov S.V., Li L., Pisters P.W., Lazar A.J., Yu D., Pollock R.E., and Lev D. Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation. Mol. Cancer Ther. 6 (2007) 1650-1660
30. Henning W., and Sturzbecher H.W. Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. Toxicology 193 (2003) 91-109
31. Raderschall E., Bazarov A., Cao J., Lurz R., Smith A., Mann W., Ropers H.H., Sedivy J.M., Golub E.I., Fritz E., and Haaf T. Formation of higher-order nuclear Rad51 structures is functionally linked to p21 expression and protection from DNA damage-induced apoptosis. J. Cell Sci. 115 (2002) 153-164
32. Holzen T.M., Shah P.P., Olivares H.A., and Bishop D.K. Tid1/Rdh54 promotes dissociation of Dmc1 from nonrecombinogenic sites on meiotic chromatin. Genes Dev. 20 (2006) 2593-2604
33. Raderschall E., Stout K., Freier S., Suckow V., Schweiger S., and Haaf T. Elevated levels of Rad51 recombination protein in tumor cells. Cancer Res. 62 (2002) 219-225
34. Fan R., Kumaravel T.S., Jalali F., Marrano P., Squire J.A., and Bristow R.G. Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression. Cancer Res. 64 (2004) 8526-8533
35. Bagrintseva K., Geisenhof S., Kern R., Eichenlaub S., Reindl C., Ellwart J.W., Hiddemann W., and Spiekermann K. FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L). Blood 105 (2005) 3679-3685
36. Slupianek A., Hoser G., Majsterek I., Bronisz A., Malecki M., Blasiak J., Fishel R., and Skorski T. Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Mol. Cell. Biol. 22 (2002) 4189-4201
37. Flygare J., Falt S., Ottervald J., Castro J., Dackland A.L., Hellgren D., and Wennborg A. Effects of HsRad51 overexpression on cell proliferation, cell cycle progression, and apoptosis. Exp. Cell Res. 268 (2001) 61-69
38. Han H., Bearss D.J., Browne L.W., Calaluce R., Nagle R.B., and Von Hoff D.D. Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res. 62 (2002) 2890-2896
39. Maacke H., Jost K., Opitz S., Miska S., Yuan Y., Hasselbach L., Luttges J., Kalthoff H., and Sturzbecher H.W. DNA repair and recombination factor Rad51 is over-expressed in human pancreatic adenocarcinoma. Oncogene 19 (2000) 2791-2795
40. Maacke H., Opitz S., Jost K., Hamdorf W., Henning W., Kruger S., Feller A.C., Lopens A., Diedrich K., Schwinger E., and Sturzbecher H.W. Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer. Int. J. Cancer 88 (2000) 907-913
41. Martin R.W., Orelli B.J., Yamazoe M., Minn A.J., Takeda S., and Bishop D.K. RAD51 up-regulation bypasses BRCA1 function and is a common feature of BRCA1-deficient breast tumors. Cancer Res. 67 (2007) 9658-9665
42. Vispe S., Cazaux C., Lesca C., and Defais M. Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation. Nucleic Acids Res. 26 (1998) 2859-2864
43. Arnaudeau C., Helleday T., and Jenssen D. The RAD51 protein supports homologous recombination by an exchange mechanism in mammalian cells. J. Mol. Biol. 289 (1999) 1231-1238
44. Arnaudeau C., Rozier L., Cazaux C., Defais M., Jenssen D., and Helleday T. RAD51 supports spontaneous non-homologous recombination in mammalian cells, but not the corresponding process induced by topoisomerase inhibitors. Nucleic Acids Res. 29 (2001) 662-667
45. Lundin C., Schultz N., Arnaudeau C., Mohindra A., Hansen L.T., and Helleday T. RAD51 is involved in repair of damage associated with DNA replication in mammalian cells. J. Mol. Biol. 328 (2003) 521-535
46. Bertrand P., Lambert S., Joubert C., and Lopez B.S. Overexpression of mammalian Rad51 does not stimulate tumorigenesis while a dominant-negative Rad51 affects centrosome fragmentation, ploidy and stimulates tumorigenesis, in p53-defective CHO cells. Oncogene 22 (2003) 7587-7592
47. Ruksc A., Birmingham E.C., and Baker M.D. Altered DNA repair and recombination responses in mouse cells expressing wildtype or mutant forms of RAD51. DNA Repair (Amst) 6 (2007) 1876-1889
48. Richardson C., Stark J.M., Ommundsen M., and Jasin M. Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability. Oncogene 23 (2004) 546-553
49. Francis R., and Richardson C. Multipotent hematopoietic cells susceptible to alternative double-strand break repair pathways that promote genome rearrangements. Genes Dev. 21 (2007) 1064-1074
50. Hu Y., Lu X., Barnes E., Yan M., Lou H., and Luo G. Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers. Mol. Cell. Biol. 25 (2005) 3431-3442
51. Hu Y., Raynard S., Sehorn M.G., Lu X., Bussen W., Zheng L., Stark J.M., Barnes E.L., Chi P., Janscak P., Jasin M., Vogel H., Sung P., and Luo G. RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev. 21 (2007) 3073-3084
52. Ira G., Malkova A., Liberi G., Foiani M., and Haber J.E. Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell 115 (2003) 401-411
53. Kohzaki M., Hatanaka A., Sonoda E., Yamazoe M., Kikuchi K., Vu Trung N., Szuts D., Sale J.E., Shinagawa H., Watanabe M., and Takeda S. Cooperative roles of vertebrate Fbh1 and Blm DNA helicases in avoidance of crossovers during recombination initiated by replication fork collapse. Mol. Cell. Biol. 27 (2007) 2812-2820
54. Oh S.D., Lao J.P., Hwang P.Y., Taylor A.F., Smith G.R., and Hunter N. BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell 130 (2007) 259-272
55. Rockmill B., Fung J.C., Branda S.S., and Roeder G.S. The Sgs1 helicase regulates chromosome synapsis and meiotic crossing over. Curr. Biol. 13 (2003) 1954-1962
56. Wu L., and Hickson I.D. The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426 (2003) 870-874
57. Yanez R.J., and Porter A.C. Gene targeting is enhanced in human cells overexpressing hRAD51. Gene Ther. 6 (1999) 1282-1290
58. Wang J.Y., Ho T., Trojanek J., Chintapalli J., Grabacka M., Stoklosa T., Garcia F.U., Skorski T., and Reiss K. Impaired homologous recombination DNA repair and enhanced sensitivity to DNA damage in prostate cancer cells exposed to anchorage-independence. Oncogene 24 (2005) 3748-3758
59. Petalcorin M.I., Galkin V.E., Yu X., Egelman E.H., and Boulton S.J. Stabilization of RAD-51-DNA filaments via an interaction domain in Caenorhabditis elegans BRCA2. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 8299-8304
60. Davies O.R., and Pellegrini L. Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats. Nat. Struct. Mol. Biol. 14 (2007) 475-483
61. Esashi F., Galkin V.E., Yu X., Egelman E.H., and West S.C. Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2. Nat. Struct. Mol. Biol. 14 (2007) 468-474