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C. elegans TFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair
- Source :
- Communications Biology, Vol 4, Iss 1, Pp 1-12 (2021), Communications Biology, Communications Biology, 4(1):1336. Springer Nature
- Publication Year :
- 2021
-
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.<br />Hereditary mutations in TTDA/GTF2H5 cause a photosensitive form of the rare developmental disorder trichothiodystrophy, however the development of models has been hampered by mutations being lethal. Thijssen et al. show that deficiency of C. elegans TTDA ortholog GTF-2H5 is, compatible with life, in contrast to depletion of other TFIIH subunits and thus propose that this model could be used for studying the pathogenesis of trichothiodystrophy.
- Subjects :
- DNA Repair
DNA repair
DNA damage
QH301-705.5
Protein subunit
Trichothiodystrophy
Medicine (miscellaneous)
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Transcription (biology)
medicine
Animals
Biology (General)
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Transcription factor
DNA, Helminth
medicine.disease
Cell biology
Nucleotide excision repair
Transcription factor II H
General Agricultural and Biological Sciences
Transcription
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 4
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Communications Biology
- Accession number :
- edsair.doi.dedup.....5aa5e73a379471a3cb271a6eb2e4d9cb