Cell cycle and mitosis | 2C: 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, neither replicating their DNA nor dividing; examples are neurons and muscle cells.
$G_{1}$ involves cell growth and organelle production, while $S$ is the synthesis phase where DNA and centrioles replicate.
During $G_{2}$ , the cell continues to grow and prepare for mitosis.
In the final $M$ phase, cells undergo mitosis.

Interphase merges $G_{1}$ , $S$ , and $G_{2}$ —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, effectively 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 serve as microtubule-organizing centers that initiate the formation of asters—radial arrays of microtubules—which in turn contribute to building the spindle apparatus. The spindle is an intricate 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, providing the attachment site for spindle fibers.

Spindle fibers attach to kinetochores on sister chromatids during prometaphase.

During the early stages of mitosis, the nuclear membrane undergoes breakdown, allowing the spindle to access the chromosomes. Later, as mitosis concludes, the nuclear envelope is reassembled around the segregated chromatids, restoring the nucleus in each daughter cell.

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

Growth arrest

Cells can stall their cycle (growth arrest) if there is substantial genetic damage(will stop in M phrase). Contact inhibition occurs when epithelial cells signal that the available space has maxed out (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) that form complexes driving 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, while tumor suppressor proteins like p53 and retinoblastoma protein (Rb) monitor and regulate these processes by inducing cell cycle arrest or apoptosis in the presence of DNA damage or other cellular stresses.

Signaling pathways including PI3K/AKT and MAPK modulate the activities of these regulatory molecules to integrate 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 allow cells to bypass checkpoints, resulting in unchecked and rapid cell division. This deregulation, combined with aberrant activation of signaling pathways like PI3K/AKT and MAPK, contributes to the development of genomic instability and the accumulation of further mutations.

As a result, cancer cells divide uncontrollably, leading to tumor formation and metastasis. This failure in regulation also hampers immune recognition and elimination of aberrant cells, exacerbating cancer progression. These disruptions—hallmarks of cancer—have spurred the development of targeted therapies, including CDK inhibitors and drugs that restore p53 function, offering promising strategies to reestablish proper cell cycle control and combat 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.