DNA Repair Helicase: a Component of BTF2 (TFIIH) Basic Transcription Factor

Abstract

The human BTF2 basic transcription factor (also called TFIIH), which is similar to the delta factor in rat and factor b in yeast, is required for class II gene transcription. A strand displacement assay was used to show that highly purified preparation of BTF2 had an adenosine triphosphate-dependent DNA helicase activity, in addition to the previously characterized carboxyl-terminal domain kinase activity. Amino acid sequence analysis of the tryptic digest generated from the 89-kilodalton subunit of BTF2 indicated that this polypeptide corresponded to the ERCC-3 gene product, a presumed helicase implicated in the human DNA excision repair disorders xeroderma pigmentosum and Cockayne's syndrome. These findings suggest that transcription and nucleotide excision repair may share common factors and hence may be considered to be functionally related.

TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer

“…HBx decreases p53 binding to XPB (Wang et al, 1994), which is both involved in nucleotide excision repair and in transcription as a basic transcription factor (Schaeffer et al, 1993), and interacts with various other DNA repair-associated proteins or enzymes, including DNA helicases (Qadri et al, 1996;Jia et al, 1997). HBx itself has been shown to attenuate nucleotide excision repair and alter the AFB 1 -induced mutation spectrum (Becker et al, 1998;Groisman et al, 1999;Jia et al, 1999;Mathonnet et al, 2004).…”

DNA repair, DNA replication and human disorders: A personal journey

“…We still do not really know the complete answer to this, though there have of course been some major advances. The first was the cloning of the ERCC2 gene by Christine Webber and Larry Thompson and demonstration that this was the XPD gene [61], the second was the seminal discovery by the group of Jean-Marc Egly in collaboration with the Rotterdam group that XPB and XPD were components of the transcription factor TFIIH, which had two functions, in NER and transcription [62]. Following on from these exciting findings we were able to identify the first mutations in the XPD gene, in TTD patients [63], and subsequently in many others and, importantly, we were able to show that each mutation site is disease-specific.…”

Nucleotide excision repair “a legacy of creativity”

“…An emerging challenge is to understand how NER and other repair systems are regulated in dividing and differentiated cells, and in normal and malignant transformed cells. The discovery that several components of NER were also components of the transcription factor TFIIH was the first recognition that NER was not an isolated system [34]. Discovery that the TCR coupling factors, CSA and CSB, were involved in ubiquitination of RNA pol II [35], and that TCR also required the function of mismatch repair [36], were further indications that understanding the integration of NER into cellular regulatory pathways was important.…”

“…But the technical tools for pursuing this connection were not yet available, and this notion was soon eclipsed by the demonstration of a linkage between transcription and repair, a discovery strongly associated with the research stimulated by both Dirk Bootsma and Philip Hanawalt [34]. Only in the past few years has pursuit of the connection between DNA repair and replication resurfaced with a flurry of exciting new discoveries.…”