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Role of Genes in Regulating Cell Proliferation

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The activation of genetic changes that result in cellular transformation causes this tightly controlled mechanism to become dysregulated.

Medically reviewed by

Dr. Arpit Varshney

Published At December 13, 2023
Reviewed AtDecember 13, 2023

Introduction:

DNA replication, centrosome duplication, mitosis, and cytokinesis are only a few of the sequentially occurring, chronologically organized processes that comprise the cell cycle. Many cell-cycle regulators have been discovered by biochemical and genetic screening, and it was quickly discovered that many of the genes encoding cell-cycle regulators, including cyclins, were only transcribed during particular cell-cycle stages. As a result, "just in time" expression is probably a crucial component of the system that preserves the correct temporal sequence of cell cycle events. Recent advances in high-throughput methods for detecting transcript levels show that the cell cycle controls a significant portion of the Saccharomyces cerevisiae transcriptome (around 20 percent).

What Is the Cell Cycle? Where do Genes help in Cell Proliferation?

Complete genetic material duplication is necessary for successful cell division and equal segregation into the two daughter cells' cell bodies.

  • Gap 1.

  • Synthesis.

  • Gap 2.

  • Mitosis

These four stages of the cell cycle are historically used to define the temporal sequence of several processes seen in regularly cycling cells. In S and M stages, most duplication and segregation events occur. DNA (deoxyribonucleic acid) and centrosomes are replicated during the S phase. To create the poles of the mitotic spindle that segregate sister chromatids, duplicate centrosomes split apart. During the M phase, also known as mitosis, sister chromatid segregation begins.

Gap phases G1 and G2 were so named because they occur between the S and M phases' observed occurrences. Cells are processing information from their extracellular and intracellular surroundings to determine if circumstances are suitable for cellular division events even though no overt cellular changes or activities are visible during G1 and G2. Early G1 cells determine whether to enter a new cell cycle by interpreting external cues (such as food availability and mating pheromone). After this moment of commitment, known in Saccharomyces cerevisiae as START, cells activate the expression of centrosome and DNA replication-related genes as they enter the S phase. Cells in the G2 phase read intracellular signals from checkpoint pathways that verify the efficiency of duplication processes and the functionality of the mitotic spindle machinery. Every cell cycle event, including DNA replication, centrosome duplication, and chromosomal segregation, is a complicated process that necessitates the cooperation of several proteins to carry out the required function. Each of these intricate actions, in turn, needs to be coordinated with the others.

What Are the Genes That Help in Cell Growth And Its Controlled?

Growth factors control cell multiplication, providing signals to encourage cell cycle entrance. Necls have a role in the interaction of the cell cycle and growth factor signaling.

Measuring mRNA levels in cells has been a standard technique to determine if genes are controlled at the transcriptional level since the development of contemporary molecular biology. Measuring mRNA abundance over time in synchronous groups of cells as they go through the cell cycle is necessary to understand gene regulation at the transcriptional level for genes implicated in the cell cycle. The first genes whose expression fluctuates regularly during the cell cycle were discovered to be histones. By comparing the timing of histone mRNA expression with the timing of DNA replication throughout several cell cycles, it was possible to categorize histone gene expression as being cell cycle-regulated.

Ten more genes involved in cell cycle events were found to express themselves periodically throughout the ensuing ten years. These genes are

  • HO (The mating-type flipping process, in which MATa cells transform into MATalpha cells or vice versa, is started by an endonuclease encoded by the HO gene).

  • CDC21 (proteins whose genes control the cell division cycle. Activating the p34cdc2 protein by these genes results in the regulatory network that initiates mitosis).

  • CDC9 (CDC9 encodes two different DNA ligase I subtype. The first, which is directed towards the mitochondrion and necessary for the replication and upkeep of mitochondrial DNA, and the second, which is directed towards the nucleus and adequate for the vital cell-division function linked to this gene, are both present in the body)

  • RAD6.

  • SWI5.

  • CDC8.

  • POL1.

  • DBF4.

  • PRI1.

  • DBF2.

The definition of periodicity for each of these genes is based on the association of gene expression with an identifiable cell cycle event known to happen only once each cycle.

What Function Does Cell Cycle Regulation Play in Transcription?

As transcription and translation need a lot of energy, the first category proposes that cell cycle-regulated transcription serves as a method to use energy resources effectively. This idea is known as "just in time" transcription, where gene products that are necessary at a certain cell cycle interval are only produced when necessary. An alternative to the first explanation, known as the "Sleeping Beauty" scenario, considers the lifespan of a cell or tissue rather than the end of a single cell cycle.Active cellular division takes place during just a fraction of a cell's whole life cycle, whether it is a single yeast cell that is budding or a community of cells that make up tissues in an organism. Environmental limitations mean that microorganisms can only divide when certain parameters (such as nutrition, temperature, growth factor signalling, etc.) are present. Cell division is not possible when the environment is not conducive to it. As a result, a single cell spends a large portion of its existence in a quiescent or resting state outside of the cell cycle. Nonetheless, the cells are prepared to finish cell cycle events with the relevant genes expressed at the proper moment whenever a signal to begin cellular division is received.

What Is Cell Cycle Progression According To Gene Expression?

It might be challenging to see and comprehend multi-gene profiles. Hence, based on the expression of all cell cycle-regulated genes discovered by RFE for each cell line, we computed and showed a cell cycle index. For all three cell lines, the index linked with the advancement of the cell cycle, with G1 phase cells exhibiting low indices and G2/M phase cells exhibiting high indexes.

Conclusion:

A number of checkpoints and layers of regulatory mechanisms carefully govern a series of events that occur during cell growth. The majority of research have used huge cell populations, yet single-cell analysis is necessary for a thorough knowledge of cell dynamics and heterogeneity. We profiled the expression of 93 genes in single cells from three distinct cell lines using quantitative real-time.

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Dr. Arpit Varshney
Dr. Arpit Varshney

General Medicine

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