A cell cycle-controlled redox switch regulates the topoisomerase IV activity
Sharath Narayanan1, Balaganesh Janakiraman1, Lokesh Kumar1
1School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram 695016, Kerala, India.
Genes & Development
|June 12, 2015
Summary
A novel protein, NstA, regulates DNA decatenation by inhibiting topoisomerase IV (topo IV) during early cell cycles. Intracellular redox state oscillations control NstA activity, acting as a cell cycle switch.
Area of Science:
- Cell Biology
- Molecular Biology
- Microbiology
Background:
- Topoisomerase IV (topo IV) is crucial for resolving catenated chromosomes during cell division.
- Regulation of topo IV activity during early cell cycle stages remains unclear.
Purpose of the Study:
- To identify novel regulators of topo IV decatenation activity in Caulobacter crescentus.
- To elucidate the mechanism controlling topo IV function in early cell cycle stages.
Main Methods:
- Identification and characterization of NstA (negative switch for topo IV decatenation activity).
- Analysis of NstA binding to the ParC subunit of topo IV.
- Monitoring of intracellular redox state oscillations during the cell cycle.
Main Results:
- NstA inhibits topo IV decatenation activity by binding to its ParC subunit.
- NstA activity is dynamically regulated by intracellular redox state oscillations.
- Redox fluctuations correlate with and control NstA activity.
Conclusions:
- NstA acts as a cell cycle-specific inhibitor of topo IV.
- Intracellular redox oscillations serve as a global regulatory switch for cell cycle progression.
- This mechanism may help pathogens adapt to host immune responses by maintaining a suitable cell cycle state.
Related Concept Videos
02:02DNA Topoisomerases
37.9K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
37.9K
01:46Electron Transport Chain: Complex I and II
19.7K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
19.7K
02:53Conservative Site-specific Recombination and Phase Variation
7.4K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
7.4K
02:04Covalently Linked Protein Regulators
9.9K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.9K
02:34Inhibition of Cdk Activity
6.2K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
01:43Electron Transport Chain: Complex III and IV
9.8K
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
9.8K