Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Basal transcription defect discriminates between xeroderma pigmentosum and trichothiodystrophy in XPD patients.

Molecular cell | Jun 24, 2003

http://www.ncbi.nlm.nih.gov/pubmed/12820975

Mutations in the XPD gene result in xeroderma pigmentosum (XP) and trichothiodystrophy (TTD), the phenotypes of which are often intricate. To understand the genotype/phenotype relationship, we engineered recombinant TFIIHs in which XPD subunits carry amino acid changes found in XPD patients. We demonstrate that all the XPD mutations are detrimental for XPD helicase activity, thus explaining the NER defect. We also show that TFIIH from TTD patients, but not from XP patients, exhibits a significant in vitro basal transcription defect in addition to a reduced intracellular concentration. Moreover, when XPD mutations prevent interaction with the p44 subunit of TFIIH, transactivation directed by certain nuclear receptors is inhibited, regardless of TTD versus XP phenotype, thus explaining the overlapping symptoms. The implications of these mutations are discussed using a structural model of the XPD protein. Our study provides explanations for the nature and the severity of the various clinical features.

Pubmed ID: 12820975 RIS Download

Mesh terms: Adenosine Triphosphatases | Amino Acid Motifs | Amino Acid Sequence | Animals | Cells, Cultured | DNA Helicases | DNA Repair | DNA-Binding Proteins | Fibroblasts | Hair Diseases | HeLa Cells | Heterozygote | Humans | Insects | Models, Molecular | Point Mutation | Proteins | Recombinant Proteins | Transcription Factors | Transcription, Genetic | Transcriptional Activation | Xeroderma Pigmentosum | Xeroderma Pigmentosum Group D Protein

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.