GTF2H5 Human

GTF2H5 is a subunit of the TFIIH complex, which is essential for the initiation of transcription by RNA polymerase II. The TFIIH complex is composed of several subunits, each contributing to its dual role in transcription and DNA repair. GTF2H5, specifically, is involved in stabilizing the TFIIH complex and maintaining its structure .

During transcription, TFIIH is required for promoter opening and promoter escape, which are critical steps in the initiation phase. GTF2H5 stimulates the ATPase activity of ERCC3/XPB, another subunit of TFIIH, to trigger DNA opening .

In the context of DNA repair, TFIIH plays a pivotal role in NER, a mechanism that repairs bulky DNA lesions caused by UV radiation and chemical mutagens. GTF2H5 helps in opening the DNA around the lesion, allowing other proteins to excise the damaged oligonucleotide and replace it with a new DNA fragment .

Mutations in the GTF2H5 gene are associated with trichothiodystrophy (TTD), a rare genetic disorder characterized by brittle hair, intellectual disability, and photosensitivity. The photosensitive form of TTD is particularly linked to defects in the NER pathway, where the loss of functional GTF2H5 leads to an unstable TFIIH complex and impaired DNA repair .

Recombinant GTF2H5 is used in various research applications to study its role in transcription and DNA repair. Understanding the function and regulation of GTF2H5 can provide insights into the molecular mechanisms underlying transcriptional regulation and DNA repair processes. This knowledge is crucial for developing therapeutic strategies for diseases associated with defects in these pathways, such as cancer and genetic disorders like TTD .