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Citation
Aguilar-Fuentes, J., Fregoso, M., Herrera, M., Reynaud, E., Braun, C., Egly, J.M., Zurita, M. (2008). p8/TTDA overexpression enhances UV-irradiation resistance and suppresses TFIIH mutations in a Drosophila trichothiodystrophy model.  PLoS Genet. 4(11): e1000253.
FlyBase ID
FBrf0206304
Publication Type
Research paper
Abstract

Mutations in certain subunits of the DNA repair/transcription factor complex TFIIH are linked to the human syndromes xeroderma pigmentosum (XP), Cockayne's syndrome (CS), and trichothiodystrophy (TTD). One of these subunits, p8/TTDA, interacts with p52 and XPD and is important in maintaining TFIIH stability. Drosophila mutants in the p52 (Dmp52) subunit exhibit phenotypic defects similar to those observed in TTD patients with defects in p8/TTDA and XPD, including reduced levels of TFIIH. Here, we demonstrate that several Dmp52 phenotypes, including lethality, developmental defects, and sterility, can be suppressed by p8/TTDA overexpression. TFIIH levels were also recovered in rescued flies. In addition, p8/TTDA overexpression suppressed a lethal allele of the Drosophila XPB homolog. Furthermore, transgenic flies overexpressing p8/TTDA were more resistant to UV irradiation than were wild-type flies, apparently because of enhanced efficiency of cyclobutane-pyrimidine-dimers and 6-4 pyrimidine-pyrimidone photoproducts repair. This study is the first using an intact higher-animal model to show that one subunit mutant can trans-complement another subunit in a multi-subunit complex linked to human diseases.

PubMed ID
PubMed Central ID
PMC2576456 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Identity of p8/TTDA.
Zurita, 2009.6.18, Identity of p8/TTDA. [FBrf0208126]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Genet.
    Title
    PLoS Genetics
    Publication Year
    2005-
    ISBN/ISSN
    1553-7404 1553-7390
    Data From Reference
    Alleles (10)
    Gene Groups (2)
    Genes (14)
    Physical Interactions (6)
    Natural transposons (1)
    Insertions (5)
    Experimental Tools (1)
    Transgenic Constructs (3)