Gene expression profiling of xeroderma pigmentosum

被引：3
作者：
Bowden N.A. [1 ,2 ]
Tooney P.A. [1 ,2 ]
Scott R.J. [1 ,2 ,3 ]
机构：
[1] Hunter Medical Research Institute, John Hunter Hospital, New Lambton Heights, NSW 2305, Lookout Rd
[2] School of Biomedical Sciences, University of Newcastle
[3] Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, New Lambton Heights, NSW 2305, Lookout Rd
来源：
Hereditary Cancer in Clinical Practice | / 4卷 / 2期
关键词：
Gene expresion profiling; Nucleotide excision repair; UV-light and neurological symptoms; Xeroderma Pigmentosum;
D O I：
10.1186/1897-4287-4-2-103
中图分类号：
学科分类号：
摘要：
Xeroderma pigmentosum (XP) is a rare recessive disorder that is characterized by extreme sensitivity to UV light. UV light exposure results in the formation of DNA damage such as cyclobutane dimers and (6-4) photoproducts. Nucleotide excision repair (NER) orchestrates the removal of cyclobutane dimers and (6-4) photoproducts as well as some forms of bulky chemical DNA adducts. The disease XP is comprised of 7 complementation groups (XP-A to XP-G), which represent functional deficiencies in seven different genes, all of which are believed to be involved in NER. The main clinical feature of XP is various forms of skin cancers; however, neurological degeneration is present in XPA, XPB, XPD and XPG complementation groups. The relationship between NER and other types of DNA repair processes is now becoming evident but the exact relationships between the different complementation groups remains to be precisely determined. Using gene expression analysis we have identified similarities and differences after UV light exposure between the complementation groups XP-A, XP-C, XP-D, XP-E, XP-F, XP-G and an unaffected control. The results reveal that there is a graded change in gene expression patterns between the mildest, most similar to the control response (XP-E) and the severest form (XP-A) of the disease, with the exception of XP-D. Distinct differences between the complementation groups with neurological symptoms (XP-A, XP-D and XP-G) and without (XP-C, XP-E and XP-F) were also identified. Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.
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页码：103 / 110
页数：7
相关论文
共 24 条
[1]  
Hendrickson E.A., Insights from model systems: Cell-cycle regulation of mammalian DNA double-strand-break repairs, Am J Hum Genet, 61, pp. 795-800, (1997)
[2]  
Singer M., Berg P., Genes and Genomes: A Changing Perspective, (1991)
[3]  
Klug W.S., Cummings M.R., Concepts in Genetics, (1994)
[4]  
Weeda G.A., A mutation in the XPB/ERCC3 DNA repair transcription gene associated with trichothiodystrophy, Am J Hum Genet, 60, pp. 320-329, (1997)
[5]  
Woods C.G., DNA repair disorders, Arch Dis Child, 78, pp. 178-184, (1998)
[6]  
Bohr V.A., Smith C.A., Okumoto D.S., Hanawalt P.C., DNA repair in an active gene: Removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall, Cell, 40, pp. 359-369, (1985)
[7]  
Mellon I., Spivak G., Hanawalt P.C., Selective removal of transcription-blocking DNA damage from the transcribed strand of mammalian DHFR gene, Cell, 51, pp. 241-249, (1987)
[8]  
Van Hoffen A., Venema J., Meschini R., Van Zeeland A.A., Mullenders L.H., Transcription-coupled repair removes both cyclobutane pyrimidine dimers and 6-4 photoproducts with equal efficiency and in a sequential way from transcribed DNA in xeroderma pigmentosum group C fibroblasts, EMBO J, 14, pp. 360-367, (1995)
[9]  
Legerski R., Peterson C., Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C, Nature, 359, pp. 70-73, (1992)
[10]  
Bootsma D., Kraemer K.H., Cleaver J.E., Hoeijmakers J.H.J., Nucleotide excision repair syndromes: Xeroderma pigmentosum and trichothiodystrophy, The Genetic Basis of Human Cancer, pp. 245-274, (1998)
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