cell line. Statistical analysis was performed using a non-parametric test and determined to be significant (Spearman rank correlation coefficient = 0.7, p = 0.04). (PDF) Acknowledgments We gratefully acknowledge Dr. Changyong Feng for assistance with statistical data analysis, and Dr. Sanjay Maggirwar for help with experiments involving p300. References 1. Sadeghi H, Hitt MA (2005) Transcriptionally targeted adenovirus vectors. Current Gene Therapy 5: 411–427. 2. Saukkonen K, Hemminki A (2004) Tissue-specific promoters for cancer gene therapy. Expert Opinion on Biological Therapy 4: 683–696. 3. Maacke H, Jost K, Opitz S, Miska S, Yuan Y, et al. (2000) DNA repair and recombination factor Rad51 is over-expressed in human pancreatic adenocar- cinoma. Oncogene 19: 2791–2795. 4. Martin RW, Orelli BJ, Yamazoe M, Minn AJ, Takeda S, et al. (2007) RAD51 up-regulation bypasses BRCA1 function and is a common feature of BRCA1- deficient breast tumors. Cancer Research 67: 9658–9665. 5. Raderschall E, Stout K, Freier S, Suckow V, Schweiger S, et al. (2002) Elevated levels of Rad51 recombination protein in tumor cells. Cancer Research 62: 219–225. 6. Maacke H, Opitz S, Jost K, Hamdorf W, Henning W, et al. (2000) Over- expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer. Int J Cancer 88: 907–913. 7. Barbano R, Copetti M, Perrone G, Pazienza V, Anna Muscarella L, et al. (2010) High RAD51 mRNA expression characterize estrogen receptor-positive/ progesteron receptor-negative breast cancer and is associated with patient’s outcome. Int J Cancer. 8. Kauffmann A, Rosselli F, Lazar V, Winnepenninckx V, Mansuet-Lupo A, et al. (2008) High expression of DNA repair pathways is associated with metastasis in melanoma patients. Oncogene 27: 565–573. 9. Mitra A, Jameson C, Barbachano Y, Sanchez L, Kote-Jarai Z, et al. (2009) Overexpression of RAD51 occurs in aggressive prostatic cancer. Histopathology 55: 696–704. 10. Shammas MA, Reis RJS, Koley H, Batchu RB, Li C, et al. (2009) Dysfunctional homologous recombination mediates genomic instability and progression in myeloma. Blood 113: 2290–2297. 11. Hannay JA, Liu J, Zhu QS, Bolshakov SV, Li L, et al. (2007) Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation. Mol Cancer Ther 6: 1650–1660. 12. Baumann P, West SC (1998) Role of the human RAD51 protein in homologous recombination and double-stranded break repair. Trends in Biochemical Sciences 23: 247–251. 13. Klein HL (2008) The consequences of Rad51 overexpression for normal and tumor cells. DNA Repair 7: 686–693. 14. Thacker J (2005) The RAD51 gene family, genetic instability and cancer. Cancer Letters 219: 125–135. 15. Richardson C (2005) RAD51, genomic stability, and tumorigenesis. Cancer Letters 218: 127–139. 16. Richardson C, Stark JM, Ommundsen M, Jasin M (2004) Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability. Oncogene 23: 546–553. 17. Xia SJJ, Shammas MA, Reis RJS (1997) Elevated recombination in immortal human cells is mediated by HsRAD51 recombinase. Molecular and Cellular Biology 17: 7151–7158. 18. Hine CM, Seluanov A, Gorbunova V (2008) Use of the Rad51 promoter for targeted anti-cancer therapy. Proc Natl Acad Sci U S A 105: 20810–20815. 19. Shirakawa T (2008) The current status of adenovirus-based cancer gene therapy. Molecules and Cells 25: 462–466. 20. Parks RJ, Smith AC, Poulin KL (2009) DNA Genome Size Affects the Stability of the Adenovirus Virion. Journal of Virology 83: 2025–2028. 21. Bett AJ, Prevec L, Graham FL (1993) Packaging Capacity and Stability of Human Adenovirus Type-5 Vectors. Journal of Virology 67: 5911–5921. 22. Hasselbach L, Haase S, Fischer D, Kolberg HC, Sturzbecher HW (2005) Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur J Gynaecol Oncol 26: 589–598. 23. Yuan Y, Ye J, Dong Q, Zheng S (2004) [Structural characterization of 59 flanking regulatory region of DNA repair gene Rad51]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 21: 248–251. 24. Arias-Lopez C, Lazaro-Trueba I, Kerr P, Lord CJ, Dexter T, et al. (2006) p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene. EMBO Rep 7: 219–224. 25. Vo N, Goodman RH (2001) CREB-binding protein and p300 in transcriptional regulation. Journal of Biological Chemistry 276: 13505–13508. 26. Grossman SR (2001) p300/CBP/p53 interaction and regulation of the p53 response. Eur J Biochem 268: 2773–2778. Rad51 Targeted Adenoviral Vector Author Contributions Conceived and designed the experiments: VF MO CC CH VG AS SD. Performed the experiments: VF MO YEK. Analyzed the data: VF MO YEK SD. Contributed reagents/materials/analysis tools: CC CH VG AS. Wrote the paper: VF VG SD. 27. Hainaut P, Soussi T, Shomer B, Hollstein M, Greenblatt M, et al. (1997) Database of p53 gene somatic mutations in human tumors and cell lines: Updated compilation and future prospects. Nucleic Acids Research 25: 151–157. 28. Lu WG, Lin JY, Chen JD (2002) Expression of p14ARF overcomes tumor resistance to p53. Cancer Research 62: 1305–1310. 29. Geyer RK, Yu ZK, Maki CG (2000) The MDM2 RING-finger domain is required to promote p53 nuclear export. Nat Cell Biol 2: 569–573. 30. Honda R, Tanaka H, Yasuda H (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420: 25–27. 31. Kalthoff H, Schmiegel W, Roeder C, Kasche D, Schmidt A, et al. (1993) P53 and K- Ras Alterations in Pancreatic Epithelial-Cell Lesions. Oncogene 8: 289–298. 32. Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, et al. (1997) Recruitment of p300/CBP in p53-dependent signal pathways. Cell 89: 1175–1184. 33. Maggirwar SB, Ramirez S, Tong N, Gelbard HA, Dewhurst S (2000) Functional interplay between nuclear factor-kappaB and c-Jun integrated by coactivator p300 determines the survival of nerve growth factor-dependent PC12 cells. J Neurochem 74: 527–539. 34. Pastorcic M, Das HK (2000) Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene. J Biol Chem 275: 34938–34945. 35. Kanaya T, Kyo S, Hamada K, Takakura M, Kitagawa Y, et al. (2000) Adenoviral expression of p53 represses telomerase activity through down- regulation of human telomerase reverse transcriptase transcription. Clin Cancer Res 6: 1239–1247. 36. Kubicka S, Kuhnel F, Zender L, Rudolph KL, Plumpe J, et al. (1999) p53 represses CAAT enhancer-binding protein (C/EBP)-dependent transcription of the albumin gene. A molecular mechanism involved in viral liver infection with implications for hepatocarcinogenesis. J Biol Chem 274: 32137–32144. 37. Schug J (2008) Using TESS to predict transcription factor binding sites in DNA sequence. Current Protocols in Bioinformatics Chapter 2: Unit 2 6. 38. Iwanaga R, Komori H, Ohtani K (2004) Differential regulation of expression of the mammalian DNA repair genes by growth stimulation. Oncogene 23: 8581–8590. 39. Slupianek A, Hoser G, Majsterek I, Bronisz A, Malecki M, et al. (2002) Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Molecular and Cellular Biology 22: 4189–4201. 40. Pfitzner E, Jahne R, Wissler M, Stoecklin E, Groner B (1998) p300/CREB- binding protein enhances the prolactin-mediated transcriptional induction through direct interaction with the transactivation domain of Stat5, but does not participate in the Stat5-mediated suppression of the glucocorticoid response. Mol Endocrinol 12: 1582–1593. 41. Graham FL, Smiley J, Russell WC, Nairn R (1977) Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 36: 59–74. 42. Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25: 585–621. 43. Wyllie FS, Jones CJ, Skinner JW, Haughton MF, Wallis C, et al. (2000) Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts. Nature Genetics 24: 16–17. 44. Scheffner M, Munger K, Byrne JC, Howley PM (1991) The State of the P53 and Retinoblastoma Genes in Human Cervical-Carcinoma Cell-Lines. Proc Natl Acad Sci U S A 88: 5523–5527. 45. Morales CP, Holt SE, Ouellette M, Kaur KJ, Yan Y, et al. (1999) Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nature Genetics 21: 115–118. 46. OConnor PM, Jackman J, Bae I, Myers TG, Fan SJ, et al. (1997) Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Research 57: 4285–4300. 47. Jacobs JP, Jones CM, Baille JP (1970) Characteristics of a human diploid cell designated MRC-5. Nature 227: 168–70. 48. Bodner SM, Minna JD, Jensen SM, Damico D, Carbone D, et al. (1992) Expression of Mutant P53 Proteins in Lung-Cancer Correlates with the Class of P53 Gene Mutation. Oncogene 7: 743–749. PLoS ONE | www.plosone.org 11 December 2011 | Volume 6 | Issue 12 | e28714