The XPD subunit of TFIIH is required for transcription-associated but not DNA double-strand break-induced recombination in mammalian cells
2010 (English)In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 25, no 6, 623-629 p.Article in journal (Other academic) Published
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 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 underlie a portion of spontaneous HR events. We also report that transcription-coupled repair (TCR) defective CSB cells, 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.
Place, publisher, year, edition, pages
2010. Vol. 25, no 6, 623-629 p.
IdentifiersURN: urn:nbn:se:su:diva-39035DOI: 10.1093/mutage/geq054OAI: oai:DiVA.org:su-39035DiVA: diva2:318048