The XPD subunit of TFIIH is required for transcription-associated but not DNA double-strand break-induced recombination in mammalian cells.

Abstract

Mutations in the XPD gene can give rise to three phenotypically distinct disorders: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) or combined XP and Cockayne syndrome (CS) (XP/CS). The role of Xeroderma Pigmentosum group D protein (XPD) in nucleotide excision repair explains the increased risk of skin cancer in XP patients but not all the clinical phenotypes found in XP/CS or TTD patients. Here, we describe that the XPD-defective UV5 cell line is impaired in transcription-associated recombination (TAR), which can be reverted by the introduction of the wild-type XPD gene expressed from a vector. UV5 cells are defective in TAR, despite having intact transcription and homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Interestingly, we find reduced spontaneous HR in XPD-defective cells, suggesting that transcription underlies a portion of spontaneous HR events. We also report that transcription-coupled repair (TCR)-defective cells, mutated in the Cockayne syndrome B (CSB) protein, have a defect in TAR, but not in DSB-induced HR. However, the TAR defect may be associated with a general transcription defect in CSB-deficient cells. In conclusion, we show a novel role for the XPD protein in TAR, linking TAR with TCR.

• Authors: Linda Savolainen, Tobias Cassel, Thomas Helleday
• Journal: Mutagenesis (Mutagenesis) Vol. 25 Issue 6 Pg. 623-9 (Nov 2010) ISSN: 1464-3804 [Electronic] England
• PMID: 20833695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Subunits
• Transcription Factor TFIIH
• Xeroderma Pigmentosum Group D Protein

Topics

• Animals
• CHO Cells
• Cells, Cultured
• Cricetinae
• Cricetulus
• DNA Breaks, Double-Stranded
• DNA Repair (genetics)
• Humans
• Mammals
• Models, Biological
• Protein Subunits (metabolism, physiology)
• Recombination, Genetic (genetics)
• Transcription Factor TFIIH (chemistry, genetics, metabolism)
• Transcription, Genetic (genetics, physiology)
• Transfection
• Xeroderma Pigmentosum Group D Protein (genetics, metabolism, physiology)