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

Renata Maria Augusto Da Costa, Lydia Riou, Apuã Paquola, Carlos Frederico Martins Menck, Alain Sarasin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1359-1374
Number of pages16
JournalOncogene
Volume24
Issue number8
DOIs
StatePublished - Feb 17 2005
Externally publishedYes

Keywords

  • DNA repair
  • Microarray
  • Nucleotide excision repair
  • Trichothiodystrophy
  • UV light
  • Xeroderma pigmentosum

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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