A phylogenetically-restricted essential cell cycle progression factor in the human pathogen Candida albicans
Priya Jaitly1, Mélanie Legrand2, Abhijit Das1
1Molecular Mycology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Nature Communications
|July 22, 2022
Summary
Researchers identified six chromosomal stability (CSA) genes in Candida albicans, including a novel gene, CSA6, crucial for cell division. This discovery offers potential new antifungal drug targets against fungal pathogens.
Area of Science:
- Mycology
- Cell Biology
- Genetics
Background:
- Chromosomal instability, often stemming from cell division errors, is linked to antifungal drug resistance in fungal pathogens.
- Understanding the genetic underpinnings of chromosomal instability is crucial for developing effective antifungal strategies.
Purpose of the Study:
- To identify genes and mechanisms that maintain chromosomal stability in the human fungal pathogen Candida albicans.
- To explore novel targets for antifungal drug development.
Main Methods:
- An overexpression screen of approximately 1000 genes was performed to monitor chromosomal stability in Candida albicans.
- Analysis focused on identifying genes involved in maintaining chromosomal integrity.
Main Results:
- Six chromosomal stability (CSA) genes were identified.
- Five CSA genes are homologous to known cell division genes in other organisms.
- A novel gene, CSA6, was discovered, present only in the CUG-Ser clade of fungi, including Candida albicans.
- Csa6 protein localizes to spindle pole bodies, is essential for mitotic exit, and triggers a metaphase arrest when overexpressed.
Conclusions:
- Csa6 is an essential cell cycle progression factor unique to the CUG-Ser fungal clade.
- The CUG-Ser clade-specific CSA6 gene represents a potential novel target for antifungal drug development.
Related Concept Videos
02:34Inhibition of Cdk Activity
4.9K
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...
4.9K
02:39Positive Regulator Molecules
5.6K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.6K
02:36Cells Coordinate Growth and Proliferation
4.6K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
4.6K
01:27Molecular Factors Affecting Cell Division
3.3K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.3K
01:23Negative Regulator Molecules
35.8K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.8K
01:28The Cell Cycle Control System
3.2K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
3.2K