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PMID: 8157004 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH).

The EMBO journal ·Vol. 13 ·No. 7 ·1994-04-01 ·Pages 1645-53

van Vuuren AJ, Vermeulen W, Ma L, Weeda G, Appeldoorn E, Jaspers NG, van der Eb AJ, Bootsma D, Hoeijmakers JH, Humbert S

Abstract

ERCC3 was initially identified as a gene correcting the nucleotide excision repair (NER) defect of xeroderma pigmentosum complementation group B (XP-B). The recent finding that its gene product is identical to the p89 subunit of basal transcription factor BTF2(TFIIH), opened the possibility that it is not directly involved in NER but that it regulates the transcription of one or more NER genes. Using an in vivo microinjection repair assay and an in vitro NER system based on cell-free extracts we demonstrate that ERCC3 in BTF2 is directly implicated in excision repair. Antibody depletion experiments support the idea that the p62 BTF2 subunit and perhaps the entire transcription factor function in NER. Microinjection experiments suggest that exogenous ERCC3 can exchange with ERCC3 subunits in the complex. Expression of a dominant negative K436-->R ERCC3 mutant, expected to have lost all helicase activity, completely abrogates NER and transcription and concomitantly induces a dramatic chromatin collapse. These findings establish the role of ERCC3 and probably the entire BTF2 complex in transcription in vivo which was hitherto only demonstrated in vitro. The results strongly suggest that transcription itself is a critical component for maintenance of chromatin structure. The remarkable dual role of ERCC3 in NER and transcription provides a clue in understanding the complex clinical features of some inherited repair syndromes.

MeSH Terms
Animals DNA Repair DNA-Binding Proteins/metabolism Drosophila Proteins Humans Microinjections Transcription Factor TFIIH Transcription Factors/metabolism Transcription Factors, TFII Transcription, Genetic Xeroderma Pigmentosum/genetics,ultrastructure
Chemicals
DNA-Binding Proteins Drosophila Proteins Transcription Factors Transcription Factors, TFII Transcription Factor TFIIH hay protein, Drosophila
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
van Vuuren A J
Department of Cell Biology and Genetics, Erasmus University, The Netherlands.
Vermeulen W
Ma L
Weeda G
Appeldoorn E
Jaspers N G
van der Eb A J
Bootsma D
Hoeijmakers J H
Humbert S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-04-01
Pages
1645-53
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394995
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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