Abstract
Xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) syndromes are characterized by deficiency in nucleotide excision repair pathway, but with distinguished clinical manifestations. While XP patients exhibit a high frequency of skin cancer, TTD patients are not cancer prone. The relation between lack of DNA repair and their clinical manifestations was investigated through analysis of the transcriptional profile of 12 600 transcripts in two isogenic cell lines with different capabilities of DNA repair. These cell lines result from a stable transfection of the XPB-TTD allele into XP complementation group B fibroblasts, from an XP patient who also have clinical abnormalities corresponding to Cockayne's syndrome (CS). The microarray assays performed under normal growth conditions showed the expression of distinct groups of genes in each cell line. The UVC-transcription modulation of these cells revealed the changes in 869 transcripts. Some of these transcripts had similar modulation pattern in both cells, although with eventually different time patterns for induction or repression. However, some different ‘UVC signature’ for each cell line was also found, that is, transcripts that were specifically UV regulated depending on the DNA repair status of the cell. These results provide a detailed portrait of expression profiles that may potentially unravel the causes of the different phenotypes of XP/CS and TTD patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Alani RM, Young AZ and Shifflett CB . (2001). Proc. Natl. Acad. Sci. USA, 98, 7812–7816.
Bootsma D and Hoeijmakers JHJ . (1993). Nature, 363, 114–115.
Chen BS and Hampsey M . (2002). Curr. Biol., 12, R620–R622.
Claverie JM . (1999). Hum. Mol. Genet., 8, 1821–1832.
Costa RMA, Chiganças V, Galhardo RS, Carvalho H and Menck CFM . (2003). Biochimie, 85, 1083–1099.
Durante W . (2003). J. Cell Physiol., 195, 373–382.
Ehrhart J-C, Gosselet FP, Culerrier RM and Sarasin A . (2003). Photochem. Photobiol. Sci., 2, 825–834.
Ena P and Pinna A . (2003). Clin. Exp. Dermatol., 28, 493–495.
Gallego PM and Sarasin A . (2003). Biochimie, 85, 1073–1082.
Gaubatz S, Lindeman GJ, Ishida S, Jakoi L, Nevins JR, Livingston DM and Rempel RE . (2000). Mol. Cell, 6, 729–735.
Gentile M, Latonen L and Laiho M . (2003). Nucleic Acids Res., 31, 4779–4790.
Gross SR, Balklava Z and Griffin M . (2003). J. Invest. Dermatol., 121, 412–423.
Gudas JM, Payton M, Thukral S, Chen E, Bass M, Robinson MO and Coats S . (1999). Mol. Cell. Biol., 19, 612–622.
Haroon ZA, Lai TS, Hettasch JM, Lindberg RA, Dewhirst MW and Greenberg CS . (1999). Lab. Invest., 79, 1679–1686.
Houseweart MK, Vilaythong A, Yin XM, Turk B, Noebels JL and Myers RM . (2003). Cell Death Differ., 10, 1329–1335.
Itin PH, Sarasin A and Pittelkow MR . (2001). J. Am. Acad. Dermatol., 44, 891–920.
Keyse SM, Applegate LA, Tromvoukis Y and Tyrrell RM . (1990). Mol. Cell. Biol., 10, 4967–4969.
Kyng KJ, May A, Brosh Jr RM, Cheng WH, Chen C, Becker KG and Bohr VA . (2003). Oncogene, 22, 1135–1149.
Lehmann AR . (2003). Biochimie, 85, 1101–1111.
Levy DE and Darnell Jr JE . (2002). Nat. Rev. Mol. Cell Biol., 3, 651–662.
Li D, Turi TG, Schuck A, Freedberg IM, Khitrov G and Blumenberg M . (2001). FASEB J., 15, 2533–2535.
Mossi R and Hubscher U . (1998). Eur. J. Biochem., 254, 209–216.
Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G and Hara E . (2001). Nature, 409, 1067–1070.
Riou L, Zeng L, Chevallier-Lagente O, Stary A, Nikaido O, Taieb A, Weeda G, Mezzina M and Sarasin A . (1999). Hum. Mol. Genet., 8, 1125–1133.
Schaeffer L, Moncollin V, Roy R, Staub A, Mezzina M, Sarasin A, Weeda G, Hoeijmakers JH and Egly JM . (1994). EMBO J., 13, 2388–2392.
Schaeffer L, Roy R, Humbert S, Moncollin V, Vermeulen W, Hoeijmakers JH, Chambon P and Egly JM . (1993). Science, 260, 58–63.
Sesto A, Navarro M, Burslem F and Jorcano JL . (2001). Proc. Natl. Acad. Sci. USA, 99, 2965–2970.
Stary A and Sarasin A . (1996). Cancer Surv., 26, 155–171.
Toole BP . (2002). Glycobiology, 12, 37R–42R.
Urano T, Saito T, Tsukui T, Fujita M, Hosoi T, Muramatsu M, Ouchi Y and Inoue S . (2002). Nature, 417, 871–875.
Vaughan AT, Betti CJ and Villalobos MJ . (2002). Apoptosis, 7, 173–177.
Vermeulen W, Scott RJ, Rodgers S, Muller HJ, Cole J, Arlett CF, Kleijer WJ, Bootsma D, Hoeijakers JH and Weeda G . (1994a). Am. J. Hum. Genet., 54, 191–200.
Vermeulen W, van Vuuren AJ, Chipoulet M, Schaeffer L, Appeldoorn E, Weeda G, Jaspers NG, Priestley A, Arlett CF, Lehmann AR, Stefanini M, Mezzina M, Sarasin A, Bootsma D, Egly J-M and Hoeijmakers JHJ . (1994b). Cold Spring Harb. Symp. Quant. Biol., 59, 317–329.
Warbrick E . (2000). BioEssays, 22, 997–1006.
Weeda G, van Ham RC, Vermeulen W, Bootsma D, van der Eb AJ and Hoeijmakers JH . (1990). Cell, 62, 777–791.
Yamasaki L . (2003). Cancer Treat Res., 115, 209–239.
Yoshida Y, von Bubnoff A, Ikematsu N, Blitz IL, Tsuzuku JK, Yoshida EH, Umemori H, Miyazono K, Yamamoto T and Cho KW . (2003). Mech. Dev., 120, 629–637.
Younes A and Aggarwall BB . (2003). Cancer, 98, 458–467.
Acknowledgements
We thank Mrs Kristel Wanderdrick for her technical assistance with the Affymetrix platform. This work was supported by grants from the Ministere de la Recherche (Paris, France) and the CNRS (Paris, France) for AS and FAPESP (São Paulo, Brazil) and CNPq (Brasilia, Brazil) for CFMM. A convenium among the laboratories was supported by CAPES/COFECUB (Brasília, Brazil/Aix en Provence, France). RMAC had a fellowship from CNPq and LR received fellowships from the Association pour la Recherche sur le Cancer (Villejuif, France) and la Fondation pour la Recherche Médicale.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).
Rights and permissions
About this article
Cite this article
da Costa, R., Riou, L., Paquola, A. et al. Transcriptional profiles of unirradiated or UV-irradiated human cells expressing either the cancer-prone XPB/CS allele or the noncancer-prone XPB/TTD allele. Oncogene 24, 1359–1374 (2005). https://doi.org/10.1038/sj.onc.1208288
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1208288
Keywords
This article is cited by
-
Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression
Nature Communications (2019)
-
Differential gene expression induced by anti-cancer agent plumbagin is mediated by androgen receptor in prostate cancer cells
Scientific Reports (2018)
-
Identification of epigenetic modifications that contribute to pathogenesis in therapy-related AML: Effective integration of genome-wide histone modification with transcriptional profiles
BMC Medical Genomics (2015)
-
On the traces of XPD: cell cycle matters - untangling the genotype-phenotype relationship of XPD mutations
Cell Division (2010)