TY - JOUR
T1 - A 3' → 5' XPB helicase defect in repair/transcription factor TFIIH of xeroderma pigmentosum group B affects both DNA repair and transcription
AU - Hwang, Jae Ryoung
AU - Moncollin, Vincent
AU - Vermeulen, Wim
AU - Seroz, Thierry
AU - Van Vuuren, Hanneke
AU - Hoeijmakers, Jan H.J.
AU - Egly, Jean Marc
PY - 1996
Y1 - 1996
N2 - XPB is a subunit of the basal transcription factor TFIIH, which is also involved in nucleotide excision repair (NER) and potentially in cell cycle regulation. A frameshift mutation in the 3'-end of the XPB gene is responsible for a concurrence of two disorders: xeroderma pigmentosum (XP) and Cockayne's syndrome (CS). We have isolated TFIIH from cells derived from a patient (XP11BE) who carries this frameshift mutation (TFI-IHmut) and from the mother of this patient (TFIIHwt) to determine the biochemical consequences of the mutation. Although identical in composition and stoichiometry to TFIIHwt, TFIIHmut shows a reduced 3' → 5' XPB helicase activity. A decrease in helicase and DNA-dependent ATPase activities was also observed with the mutated recombinant XPB protein. The XPB mutation causes a severe NER defect. In addition, we provide evidence for a decrease in basal transcription activity in vitro. The latter defect may provide an explanation for many of the XP and CS symptoms that are difficult to rationalize based solely on an NER defect. Thus, this work presents the first detailed analysis of a naturally occurring mutation in a basal transcription factor and supports the concept that the combined XP/CS clinical entity is actually the result of a combined transcription/repair deficiency.
AB - XPB is a subunit of the basal transcription factor TFIIH, which is also involved in nucleotide excision repair (NER) and potentially in cell cycle regulation. A frameshift mutation in the 3'-end of the XPB gene is responsible for a concurrence of two disorders: xeroderma pigmentosum (XP) and Cockayne's syndrome (CS). We have isolated TFIIH from cells derived from a patient (XP11BE) who carries this frameshift mutation (TFI-IHmut) and from the mother of this patient (TFIIHwt) to determine the biochemical consequences of the mutation. Although identical in composition and stoichiometry to TFIIHwt, TFIIHmut shows a reduced 3' → 5' XPB helicase activity. A decrease in helicase and DNA-dependent ATPase activities was also observed with the mutated recombinant XPB protein. The XPB mutation causes a severe NER defect. In addition, we provide evidence for a decrease in basal transcription activity in vitro. The latter defect may provide an explanation for many of the XP and CS symptoms that are difficult to rationalize based solely on an NER defect. Thus, this work presents the first detailed analysis of a naturally occurring mutation in a basal transcription factor and supports the concept that the combined XP/CS clinical entity is actually the result of a combined transcription/repair deficiency.
UR - http://www.scopus.com/inward/record.url?scp=0030570316&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.27.15898
DO - 10.1074/jbc.271.27.15898
M3 - Article
C2 - 8663148
AN - SCOPUS:0030570316
SN - 0021-9258
VL - 271
SP - 15898
EP - 15904
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 27
ER -