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  • Original Paper
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Transcriptional profiles of unirradiated or UV-irradiated human cells expressing either the cancer-prone XPB/CS allele or the noncancer-prone XPB/TTD allele

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.

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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.

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Correspondence to Alain Sarasin.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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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

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