Cell cycle and mitosis | Processes of cell division, differentiation, and specialization | Bio/biochem

The phases of the cell cycle are $G_{0}$ , $G_{1}$ , $S$ , $G_{2}$ , and $M$ .

In $G_{0}$ , cells are quiescent: they are not replicating their DNA and not dividing. Examples include neurons and muscle cells.
$G_{1}$ involves cell growth and organelle production, while $S$ is the synthesis phase in which DNA and centrioles replicate.
During $G_{2}$ , the cell continues to grow and prepares for mitosis.
In the final $M$ phase, cells undergo mitosis.
Interphase combines $G_{1}$ , $S$ , and $G_{2}$ . This is a period of intense metabolic activity and preparation for cell division.

Mitosis itself is further divided into:

Prophase: Chromatin condenses into distinct chromosomes, the nuclear membrane disassembles, and the mitotic spindle begins forming, with centriole pairs migrating to opposite poles.
Metaphase: Chromosomes align at the cell’s midline; spindle fibers attach to kinetochores located at each chromosome’s centromere.
Anaphase: Sister chromatids separate and are pulled toward opposite poles by the spindle apparatus.
Telophase: Chromosomes decondense, the nuclear membrane re-forms around each set of chromosomes, and the mitotic spindle disassembles, essentially reversing prophase.

Steps of mitosis showing the sequence of stages in cell division

Mitotic structures

During mitosis, several key structures work together:

At the cell poles, centrioles act as microtubule-organizing centers. They help form asters (radial arrays of microtubules), which contribute to building the spindle apparatus. The spindle is a network of microtubules and associated proteins that attaches to chromosomes and is responsible for pulling apart and guiding chromatids to each daughter cell.

Each chromosome is made up of two identical chromatids joined at the centromere. At the centromere, a specialized protein complex called the kinetochore forms and provides the attachment site for spindle fibers.

Spindle fibers attach to kinetochores on sister chromatids during prometaphase.

Early in mitosis, the nuclear membrane breaks down so the spindle can access the chromosomes. As mitosis concludes, the nuclear envelope is reassembled around the separated chromatids, restoring a nucleus in each daughter cell.

Chromosome movement is driven by the dynamic instability of microtubules and the action of motor proteins. Together, these mechanisms ensure chromatids are pulled accurately to opposite poles.

Growth arrest

Cells can stall the cell cycle (growth arrest) if there is substantial genetic damage (this can stop the cycle in the M phase). Contact inhibition occurs when epithelial cells signal that available space has been maximized (cells are touching). Growth arrest can also be triggered when nutrients are insufficient.

Control of cell cycle

Control of the cell cycle in eukaryotic cells is governed by a network of cyclins and cyclin-dependent kinases (CDKs). These proteins form complexes that drive the cell through its distinct phases: $G_{1}$ (growth), $S$ (DNA synthesis), $G_{2}$ (further growth and preparation), and $M$ (mitosis).

Critical checkpoints, such as the $G_{1}$ / $S$ and $G_{2}$ / $M$ transitions, assess DNA integrity and cellular readiness. Tumor suppressor proteins like p53 and retinoblastoma protein (Rb) help regulate these checkpoints by inducing cell cycle arrest or apoptosis when DNA damage or other cellular stresses are present.

Signaling pathways including PI3K/AKT and MAPK modulate the activity of these regulatory molecules. This integrates external growth signals with internal cell cycle progression, ensuring that division occurs only when conditions are optimal.

Control of the cell cycle showing checkpoints and cyclins

Loss of cell cycle controls in cancer cells

Cancer cells often lose normal cell cycle control due to disruptions in regulatory mechanisms. Mutations in genes coding for cyclins, CDKs, or tumor suppressor proteins such as p53 and Rb can allow cells to bypass checkpoints, resulting in unchecked and rapid cell division. This deregulation, combined with abnormal activation of signaling pathways like PI3K/AKT and MAPK, contributes to genomic instability and the accumulation of additional mutations.

As a result, cancer cells divide uncontrollably, leading to tumor formation and metastasis. This failure in regulation can also hamper immune recognition and elimination of abnormal cells, worsening cancer progression. These disruptions - hallmarks of cancer - have motivated targeted therapies, including CDK inhibitors and drugs that restore p53 function, which aim to reestablish proper cell cycle control and limit tumor growth.

Biosignaling

Biosignaling involves two critical types of genes that regulate cell proliferation:

Oncogenes are genes that drive cell division, and when they become dysregulated, they can lead to cancer (for example, RAS and MYC).
In contrast, tumor suppressor genes act as a brake on cell proliferation and promote apoptosis; when these genes malfunction, such as with p53 and Rb, cancer can develop.

Phases of the cell cycle

$G_{0}$ : quiescent, non-dividing state (e.g., neurons, muscle)
$G_{1}$ : cell growth, organelle production
$S$ : DNA and centriole replication
$G_{2}$ : further growth, preparation for mitosis
$M$ : mitosis (cell division)
Interphase: combined $G_{1}$ , $S$ , $G_{2}$ ; intense metabolic activity

Mitosis stages

Prophase: chromatin condenses, nuclear membrane breaks down, spindle forms, centrioles to poles
Metaphase: chromosomes align at midline, spindle fibers attach to kinetochores at centromeres
Anaphase: sister chromatids separate, pulled to opposite poles
Telophase: chromosomes decondense, nuclear membrane reforms, spindle disassembles

Mitotic structures

Centrioles: microtubule-organizing centers, form asters and spindle apparatus
Spindle: network of microtubules, pulls chromatids apart
Chromosomes: two sister chromatids joined at centromere, kinetochore attaches spindle fibers
Chromosome movement: driven by microtubule dynamics and motor proteins

Growth arrest

Cell cycle stalls with genetic damage, nutrient deficiency, or contact inhibition
Can occur at M phase or other checkpoints

Control of cell cycle

Regulated by cyclins and cyclin-dependent kinases (CDKs)
Checkpoints: $G_{1}$ / $S$ and $G_{2}$ / $M$ assess DNA integrity and readiness
Tumor suppressors (p53, Rb): induce arrest or apoptosis if damage detected
Signaling pathways (PI3K/AKT, MAPK): integrate external and internal signals

Loss of cell cycle controls in cancer cells

Mutations in cyclins, CDKs, p53, Rb disrupt checkpoints
Leads to uncontrolled division, tumor formation, metastasis
Targeted therapies: CDK inhibitors, drugs restoring p53 function

Biosignaling

Oncogenes: promote cell division (e.g., RAS, MYC); dysregulation leads to cancer
Tumor suppressor genes: inhibit proliferation, promote apoptosis (e.g., p53, Rb); malfunction enables cancer development

The phases of the cell cycle are $G_{0}$ , $G_{1}$ , $S$ , $G_{2}$ , and $M$ .

In $G_{0}$ , cells are quiescent: they are not replicating their DNA and not dividing. Examples include neurons and muscle cells.
$G_{1}$ involves cell growth and organelle production, while $S$ is the synthesis phase in which DNA and centrioles replicate.
During $G_{2}$ , the cell continues to grow and prepares for mitosis.
In the final $M$ phase, cells undergo mitosis.
Interphase combines $G_{1}$ , $S$ , and $G_{2}$ . This is a period of intense metabolic activity and preparation for cell division.

Mitosis itself is further divided into:

Prophase: Chromatin condenses into distinct chromosomes, the nuclear membrane disassembles, and the mitotic spindle begins forming, with centriole pairs migrating to opposite poles.
Metaphase: Chromosomes align at the cell’s midline; spindle fibers attach to kinetochores located at each chromosome’s centromere.
Anaphase: Sister chromatids separate and are pulled toward opposite poles by the spindle apparatus.
Telophase: Chromosomes decondense, the nuclear membrane re-forms around each set of chromosomes, and the mitotic spindle disassembles, essentially reversing prophase.

Mitotic structures

During mitosis, several key structures work together:

At the cell poles, centrioles act as microtubule-organizing centers. They help form asters (radial arrays of microtubules), which contribute to building the spindle apparatus. The spindle is a network of microtubules and associated proteins that attaches to chromosomes and is responsible for pulling apart and guiding chromatids to each daughter cell.

Growth arrest

Control of cell cycle

Loss of cell cycle controls in cancer cells

Biosignaling

Biosignaling involves two critical types of genes that regulate cell proliferation:

Oncogenes are genes that drive cell division, and when they become dysregulated, they can lead to cancer (for example, RAS and MYC).
In contrast, tumor suppressor genes act as a brake on cell proliferation and promote apoptosis; when these genes malfunction, such as with p53 and Rb, cancer can develop.

Phases of the cell cycle

$G_{0}$ : quiescent, non-dividing state (e.g., neurons, muscle)
$G_{1}$ : cell growth, organelle production
$S$ : DNA and centriole replication
$G_{2}$ : further growth, preparation for mitosis
$M$ : mitosis (cell division)
Interphase: combined $G_{1}$ , $S$ , $G_{2}$ ; intense metabolic activity

Mitosis stages

Prophase: chromatin condenses, nuclear membrane breaks down, spindle forms, centrioles to poles
Metaphase: chromosomes align at midline, spindle fibers attach to kinetochores at centromeres
Anaphase: sister chromatids separate, pulled to opposite poles
Telophase: chromosomes decondense, nuclear membrane reforms, spindle disassembles

Mitotic structures

Centrioles: microtubule-organizing centers, form asters and spindle apparatus
Spindle: network of microtubules, pulls chromatids apart
Chromosomes: two sister chromatids joined at centromere, kinetochore attaches spindle fibers
Chromosome movement: driven by microtubule dynamics and motor proteins

Growth arrest

Cell cycle stalls with genetic damage, nutrient deficiency, or contact inhibition
Can occur at M phase or other checkpoints

Control of cell cycle

Regulated by cyclins and cyclin-dependent kinases (CDKs)
Checkpoints: $G_{1}$ / $S$ and $G_{2}$ / $M$ assess DNA integrity and readiness
Tumor suppressors (p53, Rb): induce arrest or apoptosis if damage detected
Signaling pathways (PI3K/AKT, MAPK): integrate external and internal signals

Loss of cell cycle controls in cancer cells

Mutations in cyclins, CDKs, p53, Rb disrupt checkpoints
Leads to uncontrolled division, tumor formation, metastasis
Targeted therapies: CDK inhibitors, drugs restoring p53 function

Biosignaling

Oncogenes: promote cell division (e.g., RAS, MYC); dysregulation leads to cancer
Tumor suppressor genes: inhibit proliferation, promote apoptosis (e.g., p53, Rb); malfunction enables cancer development

The phases of the cell cycle are $G_{0}$ , $G_{1}$ , $S$ , $G_{2}$ , and $M$ .

In $G_{0}$ , cells are quiescent: they are not replicating their DNA and not dividing. Examples include neurons and muscle cells.
$G_{1}$ involves cell growth and organelle production, while $S$ is the synthesis phase in which DNA and centrioles replicate.
During $G_{2}$ , the cell continues to grow and prepares for mitosis.
In the final $M$ phase, cells undergo mitosis.
Interphase combines $G_{1}$ , $S$ , and $G_{2}$ . This is a period of intense metabolic activity and preparation for cell division.

Mitosis itself is further divided into:

Prophase: Chromatin condenses into distinct chromosomes, the nuclear membrane disassembles, and the mitotic spindle begins forming, with centriole pairs migrating to opposite poles.
Metaphase: Chromosomes align at the cell’s midline; spindle fibers attach to kinetochores located at each chromosome’s centromere.
Anaphase: Sister chromatids separate and are pulled toward opposite poles by the spindle apparatus.
Telophase: Chromosomes decondense, the nuclear membrane re-forms around each set of chromosomes, and the mitotic spindle disassembles, essentially reversing prophase.

Mitotic structures

During mitosis, several key structures work together:

At the cell poles, centrioles act as microtubule-organizing centers. They help form asters (radial arrays of microtubules), which contribute to building the spindle apparatus. The spindle is a network of microtubules and associated proteins that attaches to chromosomes and is responsible for pulling apart and guiding chromatids to each daughter cell.

Growth arrest

Control of cell cycle

Loss of cell cycle controls in cancer cells

Biosignaling

Biosignaling involves two critical types of genes that regulate cell proliferation:

Oncogenes are genes that drive cell division, and when they become dysregulated, they can lead to cancer (for example, RAS and MYC).
In contrast, tumor suppressor genes act as a brake on cell proliferation and promote apoptosis; when these genes malfunction, such as with p53 and Rb, cancer can develop.

Phases of the cell cycle

$G_{0}$ : quiescent, non-dividing state (e.g., neurons, muscle)
$G_{1}$ : cell growth, organelle production
$S$ : DNA and centriole replication
$G_{2}$ : further growth, preparation for mitosis
$M$ : mitosis (cell division)
Interphase: combined $G_{1}$ , $S$ , $G_{2}$ ; intense metabolic activity

Mitosis stages

Prophase: chromatin condenses, nuclear membrane breaks down, spindle forms, centrioles to poles
Metaphase: chromosomes align at midline, spindle fibers attach to kinetochores at centromeres
Anaphase: sister chromatids separate, pulled to opposite poles
Telophase: chromosomes decondense, nuclear membrane reforms, spindle disassembles

Mitotic structures

Centrioles: microtubule-organizing centers, form asters and spindle apparatus
Spindle: network of microtubules, pulls chromatids apart
Chromosomes: two sister chromatids joined at centromere, kinetochore attaches spindle fibers
Chromosome movement: driven by microtubule dynamics and motor proteins

Growth arrest

Cell cycle stalls with genetic damage, nutrient deficiency, or contact inhibition
Can occur at M phase or other checkpoints

Control of cell cycle

Regulated by cyclins and cyclin-dependent kinases (CDKs)
Checkpoints: $G_{1}$ / $S$ and $G_{2}$ / $M$ assess DNA integrity and readiness
Tumor suppressors (p53, Rb): induce arrest or apoptosis if damage detected
Signaling pathways (PI3K/AKT, MAPK): integrate external and internal signals

Loss of cell cycle controls in cancer cells

Mutations in cyclins, CDKs, p53, Rb disrupt checkpoints
Leads to uncontrolled division, tumor formation, metastasis
Targeted therapies: CDK inhibitors, drugs restoring p53 function

Biosignaling

Oncogenes: promote cell division (e.g., RAS, MYC); dysregulation leads to cancer
Tumor suppressor genes: inhibit proliferation, promote apoptosis (e.g., p53, Rb); malfunction enables cancer development