Related Experiment Video
Updated: May 12, 2025
10:59
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
3.5K
A Quinoxaline 1,4-Dioxide Activates DNA Repair Systems in Mycobacterium smegmatis: A Transcriptomic Study
Olga B Bekker1, Olesya O Galanova1,2, Aleksey A Vatlin1,3
1Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, Russia.
International Journal of Molecular Sciences
|May 7, 2025
Summary
This study reveals how tuberculosis drug LCTA-3368 affects Mycobacterium smegmatis gene expression. The drug increases DNA repair genes and reactive oxygen species, supporting its free radical-induced DNA damage mechanism.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Discovery
Background:
- Tuberculosis (TB) remains a leading infectious cause of death globally.
- Novel antitubercular agents with new mechanisms are crucial for TB therapy.
- Quinoxaline 1,4-dioxide (QdNO) derivatives show promise as antitubercular agents.
Purpose of the Study:
- To investigate the gene expression profile of Mycobacterium smegmatis exposed to the QdNO derivative LCTA-3368.
- To elucidate the mechanism of action of LCTA-3368 at the molecular level.
Main Methods:
- Exposure of M. smegmatis to varying concentrations (1/4, 1/2, 1x MIC) and durations (30, 90 min) of LCTA-3368.
- Gene expression profiling using transcriptomic analysis.
- Measurement of reactive oxygen species (ROS) levels.
Main Results:
- Significant upregulation of genes involved in DNA repair and replication.
- Altered expression of 95 genes encoding oxidoreductase proteins.
- Dose-dependent increase in reactive oxygen species upon LCTA-3368 exposure.
Conclusions:
- LCTA-3368 induces DNA repair and replication pathways in M. smegmatis.
- The mechanism of action involves free radical formation leading to DNA damage.
- Findings support the proposed antibacterial activity of QdNOs against M. smegmatis.
Related Concept Videos
01:38Nucleotide Excision Repair
3.4K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.4K
01:35Mutations
31.9K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
31.9K
01:54Base Excision Repair
21.6K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
21.6K
02:37DNA Damage can Stall the Cell Cycle
9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
02:25Overview of DNA Repair
29.4K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
29.4K
01:02Long-patch Base Excision Repair
6.9K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
6.9K