RRC ID 76072
Author Thijssen KL, van der Woude M, Davó-Martínez C, Dekkers DHW, Sabatella M, Demmers JAA, Vermeulen W, Lans H.
Title C. elegans TFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair.
Journal Commun Biol
Abstract The 10-subunit TFIIH complex is vital to transcription and nucleotide excision repair. Hereditary mutations in its smallest subunit, TTDA/GTF2H5, cause a photosensitive form of the rare developmental disorder trichothiodystrophy. Some trichothiodystrophy features are thought to be caused by subtle transcription or gene expression defects. TTDA/GTF2H5 knockout mice are not viable, making it difficult to investigate TTDA/GTF2H5 in vivo function. Here we show that deficiency of C. elegans TTDA ortholog GTF-2H5 is, however, compatible with life, in contrast to depletion of other TFIIH subunits. GTF-2H5 promotes TFIIH stability in multiple tissues and is indispensable for nucleotide excision repair, in which it facilitates recruitment of TFIIH to DNA damage. Strikingly, when transcription is challenged, gtf-2H5 embryos die due to the intrinsic TFIIH fragility in absence of GTF-2H5. These results support the idea that TTDA/GTF2H5 mutations cause transcription impairment underlying trichothiodystrophy and establish C. elegans as model for studying pathogenesis of this disease.
Volume 4(1)
Pages 1336
Published 2021-11-25
DOI 10.1038/s42003-021-02875-8
PII 10.1038/s42003-021-02875-8
PMID 34824371
PMC PMC8617094
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism DNA Repair / genetics* DNA, Helminth / physiology* Transcription Factors / genetics* Transcription Factors / metabolism
Resource
C.elegans tm6360