C. elegans TFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair

Karen L. Thijssen, Melanie van der Woude, Carlota Davó-Martínez, Dick H.W. Dekkers, Mariangela Sabatella, Jeroen A.A. Demmers, Wim Vermeulen, Hannes Lans

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

6 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Artikelnummer1336
TijdschriftCommunications Biology
Volume4
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - dec. 2021

Vingerafdruk

Duik in de onderzoeksthema's van 'C. elegans TFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair'. Samen vormen ze een unieke vingerafdruk.

Citeer dit