| 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 |
