Transcriptional profiles of unirradiated or UV-irradiated human cells expressing either the cancer-prone XPB/CS allele or the noncancer-prone XPB/TTD allele.
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.
da Costa
Renata Maria Augusto
RM
Laboratory of Genetic Instability and Cancer UPR2169 CNRS, Gustave Roussy Institute, 94805, Villejuif Cedex, France.
Riou
Lydia
L
Paquola
Apuã
A
Menck
Carlos Frederico Martins
CF
Sarasin
Alain
A
D000483:Alleles; D002460:Cell Line; D003057:Cockayne Syndrome / Q000150:complications; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D006201:Hair Diseases / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D013577:Syndrome; D014158:Transcription, Genetic / Q000528:radiation effects*; D014162:Transfection; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000235:genetics*
D004268:DNA-Binding Proteins; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases