The Cell Cycle and Cell Division
The Cell Cycle
The life of a cell, known as the cell cycle, consists of several critical events:
Begins with the formation of a cell from the division of a parent cell.
Ends with the division of the cell into two daughter cells.
Phases of the Cell Cycle
The cell cycle is divided into two main phases:
Interphase: This is the phase where cell growth and chromosome duplication occur in preparation for cell division.
Mitotic Phase (M phase): This phase involves the actual division of the cell into two identical daughter cells.
Interphase
A significant portion of the cell cycle, approximately 90%, is spent in interphase. During this time, the cell performs its routine functions.
Subphases of Interphase
Interphase is subdivided into three phases:
G1 Phase (first gap):
The cell increases in size.
The cell starts doubling its organelles in preparation for DNA replication.
S Phase (synthesis):
DNA replication occurs, resulting in two copies of each chromosome.
The copies are attached to each other as sister chromatids.
G2 Phase (second gap):
The cell continues to grow.
Preparation for cell division occurs.
End of Interphase (G2 Phase Characteristics)
At the completion of interphase:
A nuclear envelope surrounds the nucleus.
Chromosomes are duplicated during the S phase and appear uncondensed and cannot be individually seen.
Centrosomes, which duplicate to form two centrosomes, have both been formed; each consists of a pair of centrioles.
Centrosomes organize microtubules into the mitotic spindle, facilitating key mitotic events.
Mitotic Phase
Following interphase, cells transition into the mitotic phase, which consists of:
Mitosis: This involves the separation of the nucleus into two.
Cytokinesis: This involves dividing the cytoplasm to form two daughter cells.
Stages of Mitosis
Mitosis can be categorized into five distinct subphases:
Prophase/Prometaphase
Metaphase
Anaphase
Telophase
The acronym PMAT can help remember these phases.
Post-Mitosis
After mitosis is complete, the cell undergoes cytokinesis, resulting in two identical daughter cells.
Each daughter cell contains the same genetic information as the original parent cell.
Mitosis starts with a single diploid cell and ends with two diploid cells.
Understanding Diploid Cells
A diploid cell (2n) comprises two sets of chromosomes (one inherited from each parent).
Somatic cells are classified as diploid and encompass all body cells in an organism except reproductive cells (sperm and egg).
Each species possesses a characteristic diploid number. For humans, this is 46 chromosomes, expressed as 2n = 46 (2 sets of 23).
Binary Fission in Prokaryotes
Prokaryotes (including bacteria and archaea) reproduce through a cell division process known as binary fission.
The steps involved in binary fission include:
The single circular chromosome replicates, initiating at the "origin of replication."
The two daughter chromosomes actively migrate apart while the cell elongates.
The plasma membrane pinches inward, effectively separating the cell into two.
Given that prokaryotes predate eukaryotes, it is probable that mitosis evolved from the process of binary fission.
Importance of Cell Division
The ability to reproduce is a major differentiator between living organisms and inanimate matter.
The continuity of life relies on the reproduction of cells, or cell division.
In unicellular organisms, the division of one cell results in the reproduction of the entire organism.
In multicellular organisms, cell division is essential for:
Development from a fertilized egg into an embryo.
Growth of the organism.
Repair of damaged tissues and replacement of defective cells.
Control System Overview
The frequency of cell division varies among different cell types. For example:
Skin cells divide frequently.
Liver cells divide only as needed.
The sequential events of the cell cycle are directed by a cell cycle control system, which is managed at specific checkpoints regulated by internal and external signals.
Checkpoint: A control point in the cell cycle where signals can either halt or allow the cell cycle to proceed.
Generally, animal cells are equipped with intrinsic stop signals that can halt the cycle at checkpoints, until overridden by go-ahead signals.
These signals indicate whether vital cellular processes have occurred before the cell can progress to the next phase of the cell cycle.
Three major checkpoints are located in the G1, G2, and M phases.
G1 Checkpoint
The G1 checkpoint is considered the most critical in mammalian cells.
Typically, once a go-ahead signal is received here, the cell will proceed through all subsequent phases and divide.
If it does not receive a go-ahead signal, it might exit the cell cycle, entering a non-dividing state known as the G0 phase.
Non-Dividing Cells
Most specialized cells within the human body reside in the G0 phase.
Certain categories of cells, such as mature nerve and muscle cells, do not divide.
Liver cells can be reactivated from the G0 phase back into the cell cycle due to external signals, including growth factors released during injury.
G1 Checkpoint (Requirements for Progression)
The G1 checkpoint assesses whether specific conditions are satisfied before permitting the cell to advance in the cycle:
The cell has reached a sufficient size.
There is an adequate supply of resources and energy available.
There is sufficient space in the environment for more cells.
DNA is free from damage.
Key signaling molecules, including specific growth factors, must be present.
G2 Checkpoint
The G2 checkpoint verifies that DNA replication from the S phase occurred correctly.
Similar to the G1 checkpoint, it checks for adequate materials and energy supply before proceeding to the M phase.
If DNA damage is detected, repairs must be made before entering the mitotic phase. If repairs are unattainable, the cell undergoes apoptosis (programmed cell death).
M Checkpoint
The M checkpoint ensures that all kinetochores are successfully attached to the microtubules of the mitotic spindle prior to initiating anaphase.
If kinetochores are incorrectly attached, the cell halts mitosis.
Cell Cycle Regulators
The checkpoints within the cell cycle are regulated by two main categories of proteins: cyclins and cyclin-dependent kinases (CDKs).
CDKs: Enzymes that phosphorylate other proteins. These enzymes are activated only when bound to cyclins, forming cyclin-CDK complexes that allow cells to advance past checkpoints.
CDKs are consistently present in cells, while cyclins are synthesized and degraded as per the phase of the cell cycle and in response to internal and external signals (e.g., cell size, DNA damage, nutrient availability).
Consequently, the concentration and activity of CDK-cyclin complexes vary throughout the lifespan of a cell.
Regulation During the G1 Checkpoint (Stimulus)
Growth factors elevating the levels of G1 cyclins trigger the activation of CDKs, permitting the cell cycle to bypass the G1 checkpoint and divide.
Example: When an injury occurs, blood platelets secrete platelet-derived growth factor (PDGF), which binds to receptors on fibroblast cells, activating the G1 cyclin-CDK complex, and facilitating the division of these cells to aid in wound healing.
Regulation During the G1 Checkpoint (Inhibitory Signals)
When cells experience overcrowding, they send out signals that inhibit each other from dividing by suppressing CDK-cyclin complexes at the G1 checkpoint, a process termed density-dependent inhibition.
Regulation at the G2 Checkpoint (Stimulus)
A special class of cyclins known as mitotic cyclins gradually accumulate during the G2 phase when conditions are favorable.
Mitotic cyclins bind to CDKs to form the mitosis-promoting factor (MPF) complex, signaling that the cell can proceed into mitosis.
Soon after mitosis, the mitotic cyclins degrade, and the cell transitions back to the G1 phase.
Regulation at the G2 Checkpoint (Inhibitory Signals)
In the presence of DNA damage, a key protein referred to as p53 inhibits the CDK-cyclin complex, halting the cell cycle’s progression.
This pause allows for DNA repair; if unrepaired, p53 may initiate apoptosis. This protein additionally plays a similar role during the G1 checkpoint.
The Fate of Cells
Option #1: Cells respond to specific molecular signals, usually growth factors, to undergo mitosis and divide.
Option #2: Cells may receive signals prompting them to cease division to specialize in their structure and function in a process called differentiation. Some differentiated cells can divide again under certain circumstances.
Option #3: Cells might receive signals that lead to apoptosis (programmed cell death), eliminating unnecessary cells during development or unhealthy/damaged cells in mature organisms.
The Cause of Cancer
Normal developmental and tissue maintenance hinges upon a balance between signals promoting and inhibiting cell division.
Two key types of genes code for proteins that manage and control the cell cycle:
Proto-oncogenes: Genes that create proteins promoting the cell cycle.
Tumor suppressor genes: Genes that create proteins inhibiting the cell cycle and promoting apoptosis.
Mutations in these gene types can lead to unregulated cell division and tumor growth.
Mutations and Cancer Development
Mutations in proto-oncogenes can convert them into oncogenes, which produce proteins causing overstimulation of the cell cycle, akin to “putting the foot on the gas.”
Example: A mutation in a gene coding for a CDK protein could result in it becoming hyperactive, accelerating cell division.
Conversely, mutations in tumor suppressor genes result in the synthesis of proteins that fail to inhibit the cell cycle, comparable to “removing the foot from the brake.”
Example: A mutation in the gene coding for p53 might lead to its failure to inhibit inappropriate cell division—p53 mutations are associated with roughly half of human cancers.
Both forms of mutations culminate in unchecked cell division.