GTF2H4

GTF2H4 is a gene that encodes one of the subunits of the General Transcription Factor IIH (GTF IIH) complex, which plays a crucial role in nucleotide excision repair (NER) and transcription initiation by RNA polymerase II. The GTF2H4 gene is located on chromosome 6 in humans and is essential for the proper functioning of the GTF IIH complex. This complex is involved in various cellular processes, including DNA repair, transcription, and cell cycle control, highlighting the importance of GTF2H4 in maintaining genomic stability and preventing DNA damage.

Function

GTF2H4 encodes a protein that is a component of the GTF IIH core complex. This complex is necessary for the transcription of genes by RNA polymerase II, a process that is fundamental for the synthesis of messenger RNA (mRNA) and some small nuclear RNAs. The GTF IIH complex is also involved in the nucleotide excision repair pathway, which is responsible for repairing bulky helix-distorting lesions, such as those caused by ultraviolet (UV) light, thereby preventing mutations that could lead to cancer.

In addition to its roles in transcription and DNA repair, GTF2H4 and the GTF IIH complex are implicated in cell cycle regulation, particularly at the transition from the G1 phase to the S phase. This regulation ensures that DNA is not replicated before it is repaired, which is crucial for maintaining genomic integrity.

Structure

The GTF2H4 protein is a part of the GTF IIH complex, which consists of several subunits. These subunits work together to form a complex that can efficiently bind to DNA and RNA polymerase II, facilitating the initiation of transcription. The structure of GTF2H4 allows it to interact with other components of the GTF IIH complex, contributing to the complex's stability and function.

Clinical Significance

Mutations in the GTF2H4 gene can lead to defects in the GTF IIH complex, affecting its ability to participate in DNA repair and transcription. Such defects can result in a predisposition to cancer, as the accumulation of DNA damage without proper repair can lead to mutations in critical genes involved in cell growth and division. Understanding the role of GTF2H4 in DNA repair and transcription has implications for cancer research and the development of therapies targeting the DNA damage response pathway.

Research

Research on GTF2H4 and its role in the GTF IIH complex continues to provide insights into the mechanisms of transcription and DNA repair. Studies have explored the interactions between GTF2H4 and other subunits of the GTF IIH complex, as well as how mutations in GTF2H4 affect cellular processes and contribute to disease. Ongoing research aims to uncover potential therapeutic targets within the DNA repair and transcription pathways, offering hope for new treatments for cancer and other diseases associated with DNA damage and repair defects.