A functional analysis of G23A polymorphism and the alternative splicing in the expression of the XPA gene

• Autorzy: Butkiewicz D. , Krzesniak M. , Vaitiekunaite R. , Sikora B. , Bowman E.D. , Harris C.C. , Rusin M.
• Języki publikacji: EN

Abstrakty

EN

The XPA gene has a commonly occurring polymorphism (G23A) associated with cancer risk. This study assessed the functional significance of this polymorphism, which is localised near the translation start codon. Lymphoblastoid cell lines with alternative homozygous genotypes showed no significant differences in their XPA levels. The luciferase reporter assay detected no functional difference between the two sequences. Unexpectedly, we found that the alternatively spliced form of XPA mRNA lacked a part of exon 1. Only the reading frame downstream of codon Met59 was preserved. The alternative mRNA is expressed in various human tissues. The analysis of the 5’cDNA ends showed similar transcription start sites for the two forms. The in vitro expression of the alternative XPA labelled with the red fluorescent protein (mRFP) showed a lack of preferential nuclear accumulation of the XPA isoform. The biological role of the alternative XPA mRNA form remains to be elucidated.

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2010
• Tom: 15
• Numer: 4
• Opis fizyczny: p.611-629,fig.,ref.

Twórcy

autor

Butkiewicz D.

• Department of Tumor Biology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland

autor

Krzesniak M.

autor

Vaitiekunaite R.

autor

Sikora B.

autor

Bowman E.D.

autor

Harris C.C.

autor

Rusin M.

Bibliografia

• 1. Hoeijmakers, J.H.J. Genome maintenance mechanisms for preventing cancer. Nature 411 (2001) 366-374.
• 2. Cleaver, J.E. Common pathways for ultraviolet skin carcinogenesis in the repair and replication defective groups of xeroderma pigmentosum. J. Dermatol. Sci. 23 (2000) 1-11.
• 3. Cleaver, J.E. Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nat. Rev. Cancer 5 (2005) 564-573.
• 4. Kraemer, K.H., Patronas, N.J., Schiffmann, R., Brooks, B.P., Tamura, D. and DiGiovanna, J.J. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience 145 (2007) 1388-1396.
• 5. Mohrenweiser, H.W. and Jones, I.M. Variation in DNA repair is a factor in cancer susceptibility: a paradigm for the promises and perils of individual and population risk estimation? Mutat. Res. 400 (1998) 15-24.
• 6. Goode, E.L., Ulrich, C.M. and Potter, J.D. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol. Biomarkers Prev. 11 (2002) 1513-1530.
• 7. Richards, F.M., Goudie, D.R., Cooper, W.N., Jene, Q., Barroso, I., Wicking, C., Wainwright, B.J. and Ferguson-Smith, M.A. Mapping the multiple selfhealing squamous epithelioma (MSSE) gene and investigation of xeroderma pigmentosum group A (XPA) and PATCHED (PTCH) as candidate genes. Hum. Genet. 101 (1997) 317-322.
• 8. Butkiewicz, D., Rusin, M., Harris, C.C. and Chorazy, M. Identification of four single nucleotide polymorphisms in DNA repair genes: XPA and XPB (ERCC3) in Polish population. Human Mut. 15 (2000) 577-578.
• 9. Mellon, I., Hock, T., Reid, R., Porter, P.C. and States, J.C. Polymorphisms in the human xeroderma pigmentosum group A gene and their impact on cell survival and nucleotide excision repair. DNA Repair 1 (2002) 531-546.
• 10. Park, J.Y., Park, S.H., Choi, J.E., Lee, S.Y., Jeon, H.S., Cha, S.I., Kim, C.H., Park, J.H., Kam, S., Park, R.W., Kim, I.S. and Jung, T.H. Polymorphisms of the DNA repair gene xeroderma pigmentosum group and risk of primary lung cancer. Cancer Epidemiol. Biomarkers Prev. 11 (2002) 993-997.
• 11. Butkiewicz, D., Popanda, O., Risch, A., Edler, L., Dienemann, H., Schulz, V., Kayser, K., Drings, P., Bartsch, H. and Schmezer, P. Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene. Cancer Epidemiol. Biomarkers Prev. 13 (2004) 2242-2246.
• 12. Weiss, J.M., Weiss, N.S., Ulrich, C.M., Doherty, J.A., Voigt, L.F. and Chen, C. Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer. Cancer Epidemiol. Biomarkers Prev. 14 (2005) 2524- 2530.
• 13. Zienolddiny, S., Campa, D., Lind, H., Ryberg, D., Skaug, V., Stangeland, L., Phillips, D.H., Canzian, F. and Haugen, A. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis 27 (2006) 560-567.
• 14. Sugimura, T., Kumimoto, H., Tohnai, I., Fukui, T., Matsuo, K., Tsurusako, S., Mitsudo, K., Ueda, M., Tajima, K. and Ishizaki, K. Gene-environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphisms. J. Oral. Pathol. Med. 35 (2006) 11-18.
• 15. Guo, W., Zhou, R.M., Wan, L.L., Wang, N., Li, Y., Zhang, X.J. and Dong, X.J. Polymorphisms of the DNA repair gene xeroderma pigmentosum groups A and C and risk of esophageal squamous cell carcinoma in a population of high incidence region of North China. J. Cancer Res. Clin. Oncol. 134 (2008) 263-270.
• 16. Kiyohara, C. and Yoshimasu, K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis. Int. J. Med. Sci. 4 (2007) 59-71.
• 17. Gu, J., Zhao, H., Dinney, C.P., Zhu, Y., Leibovici, D., Bermejo, C.E., Grossman, H.B. and Wu, X. Nucleotide excision repair gene polymorphisms and recurrence after treatment for superficial bladder cancer. Clin. Cancer Res. 11 (2005) 1408-1415.
• 18. Feng, J., Sun, X., Sun, N., Qin, S., Li, F., Cheng, H., Chen, B., Cao, Y., Ma, J., Cheng, L., Lu, Z., Ji, J. and Zhou, Y. XPA A23G polymorphism is associated with the elevated response to platinum-based chemotherapy in advanced non-small cell lung cancer. Acta Biochim. Biophys. Sin. 41 (2009) 429-35.
• 19. Saldivar, J.S., Lu, K.H., Liang, D., Gu, J., Huang, M., Vlastos, A.T., Follen, M. and Wu, X. Moving toward individualized therapy based on NER polymorphisms that predict platinum sensitivity in ovarian cancer patients. Gynecol. Oncol. 107 (Suppl. 1), (2007) S223-S229.
• 20. Wu, X., Zhao, H., Wei, Q., Amos, C.I., Zhang, K., Guo, Z., Qiao, Y., Hong, W.K. and Spitz, M.R. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 24 (2003) 505-509.
• 21. Porter, P.C., Mellon, I. and States, J.C. XP-A cells complemented with Arg228Gln and Val234Leu polymorphic XPA alleles repair BPDE-induced DNA damage better than cells complemented with the wild type allele. DNA Repair 4 (2005) 341-349.
• 22. Campbell, R.E., Tour, O., Palmer, A.E., Steinbach, P.A., Baird, G.S., Zacharias, D.A. and Tsien, R.Y. A monomeric red fluorescent protein. Proc. Natl. Acad. Sci. USA 99 (2002) 7877-7882.
• 23. Barber, R.D., Harmer, D.W., Coleman, R.A. and Clark, B.J. GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol. Genomics 21 (2005) 389-395.
• 24. Cleaver, J.E. and States, J.C. The DNA damage-recognition problem in human and other eucaryotic cells: the XPA damage binding protein. Biochem. J. 328 (1997) 1-12.
• 25. Dusinska, M., Dzupinkova, Z., Wsolova, L., Harrington, V. and Collins, A.R. Possible involvement of XPA in repair of oxidative DNA damage deduced from analysis of damage, repair and genotype in a human population study. Mutagenesis 21 (2006) 205-211.
• 26. Swift, M., Chase, C. Cancer in families with xeroderma pigmentosum. J. Natl. Cancer Inst. 62 (1979) 1415-1421.
• 27. Kozak, M. Interpreting cDNA sequences: some insights from studies on translation. Mamm. Genome 7 (1996) 563-574.
• 28. Afshar-Khargan, V., Li, C.Q., Khoshnevis-Asl, M. and Lopez, J.A. Kozak sequence polymorphism of the glycoprotein (GP) Ibα gene is a major determinant of the plasma membrane levels of the platelet GP Ib-IX-V complex. Blood 94 (1999) 186-191.
• 29. Jacobson, E.M., Concepcion, E., Oashi, T. and Tomer Y. A Graves' diseaseassociated Kozak sequence single-nucleotide polymorphism enhances the efficiency of CD40 gene translation: a case for translational pathophysiology. Endocrinology 146 (2005) 2684-2691.
• 30. Layher, S.K. and Cleaver, J.E. Quantification of XPA gene expression levels in human and mouse cell lines by competitive RT-PCR. Mutat. Res. 383 (1997) 9-19.
• 31. Cheng, L., Guan, Y., Li, L., Legerski, R.J., Einspahr, J., Bangert, J., Alberts, D.S. and Wie, Q. Expression in normal human tissues of five nucleotide excision repair genes measured simultaneously by multiplex reverse transcription-polymerase chain reaction. Cancer Epidemiol. Biomarkers Prev. 8 (1999) 801-807.
• 32. Henke, W., Herdel, K., Jung, K., Schnorr, D. and Loening, S.A. Betaine improves the PCR amplification of GC-rich DNA sequences. Nucleic Acids Res. 25 (1997) 3957-3958.
• 33. Krzesniak, M., Butkiewicz, D., Samojedny, A., Chorazy, M. and Rusin M. Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland. Ann. Hum. Genet. 68 (2004) 300-312.
• 34. Stetefeld, J. and Ruegg, M.A. Structural and functional diversity generated by alternative mRNA splicing. Trends Biochem. Sci. 30 (2005) 515-521.
• 35. Emmert, S., Schneider, T.D., Khan, S.G. and Kraemer, K.H. The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms. Nucleic Acids Res. 29 (2001) 1443-1452.
• 36. Khan, S.G., Muniz-Medina, V., Shahlavi, T., Baker, C.C., Inui, H., Ueda, T., Emmert, S., Schneider, T.D. and Kraemer, K.H. The human XPC DNA repair gene: arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res. 30 (2002) 3624-3631.
• 37. Kang, D. and Hamasaki, N. Maintenance of mitochondrial DNA integrity: repair and degradation. Curr. Genet. 41 (2002) 311-322.
• 38. Yamaguchi, S., Shinmura, K., Saitoh, T., Takenoshita, S., Kuwano, H. and Yokota, J. A single nucleotide polymorphism at the splice donor site of the human MYH base excision repair genes results in reduced translation efficiency of its transcripts. Genes Cells 7 (2002) 461-474.
• 39. Inoki, T., Yamagami, S., Inoki, Y., Tsuru, T., Hamamoto, T., Kagawa, Y., Mori, T. and Endo, H. Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair. Biochem. Biophys. Res. Commun. 314 (2004) 1036-1043.
• 40. Tao, H., Shinmura, K., Hanaoka, T., Natsukawa, S., Shaura, K., Koizumi, Y., Kasuga, Y., Ozawa, T., Tsujinaka, T., Li, Z., Yamaguchi, S., Yokota, J., Sugimura, H. and Tsugane, S. A novel splice-site variant of the base excision repair gene MYH is associated with production of an aberrant mRNA transcript encoding a truncated MYH protein not localized in the nucleus. Carcinogenesis 25 (2004) 1859-1866.
• 41. Tanioka, M., Budiyant, A., Ueda, T., Nagano, T., Ichihashi, M., Miyachi, Y. and Nishigori, C. A novel XPA gene mutation and its functional analysis in a Japanese patient with xeroderma pigmentosum group A. J. Invest. Dermatol. 125 (2005) 244-246.

Uwagi

PL

Rekord w opracowaniu.