Related Experiment Video
Updated: Aug 13, 2026
11:27
X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
p8/TTD-A as a repair-specific TFIIH subunit
Frédéric Coin1, Luca Proietti De Santis, Tiziana Nardo
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université Louis Pasteur, BP 163, 67404 Illkirch Cedex, C. U. Strasbourg, France. fredr@igbmc.u-strasbg.fr
Molecular Cell
|January 24, 2006
Summary
The TFIIH subunit p8/TTD-A is vital for DNA repair by initiating DNA opening, facilitating lesion removal. It is not essential for transcription and can even rescue cells with XPD mutations.
Area of Science:
- Molecular Biology
- DNA Repair Mechanisms
- Gene Transcription Regulation
Background:
- The transcription/repair factor TFIIH is a multi-subunit complex essential for both gene transcription and DNA repair.
- Understanding the specific roles of individual TFIIH subunits is crucial for elucidating its complex functions.
- The tenth subunit, p8/TTD-A, has an incompletely defined role within the TFIIH complex.
Purpose of the Study:
- To elucidate the specific functions of the TFIIH subunit p8/TTD-A in DNA repair and transcription.
- To investigate how p8/TTD-A interacts with other factors to direct TFIIH activity.
- To determine the therapeutic potential of p8/TTD-A in conditions with TFIIH-related defects.
Main Methods:
- Fluorescent antibody labeling to visualize protein localization at DNA damage sites.
- Biochemical assays to assess ATPase activity stimulation.
- Cellular complementation assays using TTD-XPD cells to evaluate functional rescue.
Main Results:
- p8/TTD-A stimulates XPB ATPase activity in conjunction with XPC-hHR23B, triggering DNA opening essential for XPA recruitment during DNA repair.
- p8/TTD-A is dispensable for RNA synthesis and does not impede the transcriptional function of CAK.
- Overexpression of p8 in TTD-XPD cells restores TFIIH concentration and counteracts the negative effects of XPD mutations.
Conclusions:
- p8/TTD-A plays a critical, specific role in initiating DNA repair by facilitating DNA opening.
- p8/TTD-A's function is distinct from its role in transcription, highlighting subunit-specific roles within TFIIH.
- p8/TTD-A has potential as a therapeutic target to restore cellular function in TFIIH-related disorders.
Related Concept Videos
02:10Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
02:36Transfer RNA Synthesis
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:30General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:41Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...