Drosophila as a Model Organism to Understand the Effects during Development of TFIIH-Related Human Diseases.

Mario Zurita,Juan Manuel Murillo-Maldonado

doi:10.3390/ijms21020630

Abstract

Human mutations in the transcription and nucleotide excision repair (NER) factor TFIIH are linked with three human syndromes: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS). In particular, different mutations in the XPB, XPD and p8 subunits of TFIIH may cause one or a combination of these syndromes, and some of these mutations are also related to cancer. The participation of TFIIH in NER and transcription makes it difficult to interpret the different manifestations observed in patients, particularly since some of these phenotypes may be related to problems during development. TFIIH is present in all eukaryotic cells, and its functions in transcription and DNA repair are conserved. Therefore, Drosophila has been a useful model organism for the interpretation of different phenotypes during development as well as the understanding of the dynamics of this complex. Interestingly, phenotypes similar to those observed in humans caused by mutations in the TFIIH subunits are present in mutant flies, allowing the study of TFIIH in different developmental processes. Furthermore, studies performed in Drosophila of mutations in different subunits of TFIIH that have not been linked to any human diseases, probably because they are more deleterious, have revealed its roles in differentiation and cell death. In this review, different achievements made through studies in the fly to understand the functions of TFIIH during development and its relationship with human diseases are analysed and discussed.

Highlights

The transcription of genes that encode messenger RNAs, long non-coding RNAs and micro-RNA precursors in eukaryotic cells is conducted by the RNA polymerase II (RNPII) enzyme [1]
Among the pre-initiation complex (PIC) components, the TFIIH complex participates in transcription by RNPII and RNA polymerase I (RNPI), as well as in DNA repair, and one of its subcomplexes participates in cell cycle control (Figure 1)
Characterization of the nature of different p52 mutant alleles allowed the generation of these mutations in human p52, which were introduced into insect culture cells, co-expressed with all the other components of the TFIIH complex and assayed in in vitro experiments to determine the effect of these mutations on transcription and DNA repair [35]

Summary

Introduction

The transcription of genes that encode messenger RNAs, (mRNAs), long non-coding RNAs (lncRNAs) and micro-RNA (miRNA) precursors in eukaryotic cells is conducted by the RNA polymerase II (RNPII) enzyme [1]. Mouse models to study the effects of mutations in the p8, XPD and XPB TFIIH subunits were developed and used to understand how these mutations identified in humans affect mouse physiology.

Results

Conclusion