DNA dynamics and types of division
The understanding of the cycle is based on changes in the amount of DNA, which is denoted by the Latin letter n (haploid set, typical of mature gametes). Most somatic cells of our body are diploid (2n).
There are two main types of division:
- Mitosis. This is the standard method by which somatic cells and early germline precursors multiply. The cell prepares by doubling its DNA to a tetraploid state (4n) and then divides, forming two exact copies, each with a 2n set.
- Meiosis. A specific process occurring only during the formation of gametes (oocytes and spermatocytes at the final stages of development). The first meiotic division is similar to mitosis (a 4n cell yields two 2n cells). The main difference lies in the second division: it starts without prior DNA duplication, resulting in the formation of four haploid cells (n).
Periods of the mitotic cycle
For cells capable of division, the life cycle is identical to the mitotic cycle. It consists of the division period itself (mitosis) and a lengthy preparation for it — interphase.
Interphase includes three phases:
- $G_1$ (presynthetic phase). Begins immediately after mitosis. The cell grows and restores its cytoplasmic volume. At the end of the phase is the "restriction point": if the cell receives external signals (mitogens) and passes this point, it irreversibly prepares for the next division. DNA set — 2n.
- $S$ (synthetic phase). The main event is the replication of DNA and chromosomal proteins. The DNA set increases from 2n to 4n. Centrioles duplicate near the nucleus. Centromeric regions of chromosomes are not copied in this phase, holding chromatids together until the onset of mitotic anaphase.
- $G_2$ (postsynthetic phase). A relatively short stage before division. DNA set — 4n. The cell actively synthesizes substances for mitosis, primarily the protein tubulin, which builds the mitotic spindle.
Classification of cells by their ability to divide
Depending on proliferative activity, all cells of an adult organism can be divided into three functional groups:
- Mitotic cells. Constantly undergo the cell cycle. Examples: basal layer epidermal cells, intestinal epithelium, early blood cell precursors.
- Conditionally postmitotic cells. Normally reside in the resting phase ($G_0$), performing their routine functions. However, when necessary (e.g., for organ regeneration), they can re-enter the cycle and begin dividing. These include hepatocytes, fibroblasts, lymphocytes, as well as bone and muscle tissue stem cells.
- Postmitotic cells. Have undergone terminal differentiation and permanently lost the ability to divide. They function for a long time and then die. Clear examples include neurons, cardiomyocytes, muscle fibers, and cells of the upper epidermal layers.
Resting phase ($G_0$) and cell fate
If a cell leaves the mitotic cycle at the $G_1$ stage, it enters the resting phase — $G_0$.
Exit into $G_0$ can occur for various reasons: temporary "sleep" of stem cells, resource shortage, the need to repair DNA damage, or the onset of specialization (differentiation).
For some cells (conditionally postmitotic), this exit is reversible: under the influence of signals, they can return from $G_0$ directly into the $S$ phase.
For others (postmitotic), specialization means an irreversible exit from the cycle. For example, in the epidermis, cells shift from the basal layer to the spinous, granular, and lucidum layers, where they only function but no longer divide, and in the cornified layer — they die off. Long-lived postmitotic cells (neurons, cardiomyocytes) function throughout the organism's entire life and die either from aging or damaging factors.
Briefly: answers to topical questions
What phases does the process of mitosis include?
The process of mitosis is classically divided into four sequential division phases.
- Prophase — chromatin condensation occurs and condensed chromosomes become visible.
- Metaphase — the mitotic spindle forms, and chromosomes align at the metaphase plate along the cell equator.
- Anaphase — spindle fibers shorten, and daughter chromosomes move toward the opposite poles of the cell.
- Telophase — chromosomes reach the poles, after which the disassembly of the mitotic apparatus begins.
Which cyclin-dependent kinases and cyclins regulate cell cycle progression?
Cell cycle progression is controlled by complexes of cyclins and cyclin-dependent kinases (Cdks).
- G1/S cyclins D and E are responsible for preparing cells for DNA replication.
- Cyclins D1, D2, D3 + Cdk4/Cdk6 are necessary to overcome the restriction point; cyclin D–Cdk4 and cyclin D–Cdk6 complexes participate in initiating a new cell cycle.
- Cyclin E–Cdk2 is associated with entry into the cycle; in phase G1b, this complex phosphorylates the Rb factor, leading to E2F activation.
- Cyclin A–Cdk2 triggers the S phase and initiates DNA replication.
- Cyclin B–Cdk1 ensures the transition to mitosis and participates in triggering mitosis.
After the controlled phase is completed, cyclins undergo degradation; cyclin destruction occurs via ubiquitination, and degradation in proteasomes has also been described.
What factors cause apoptosis during cell cycle disruptions?
During mitotic cycle disruptions, apoptosis ("from internal triggers") is caused by uncorrectable defects detected at checkpoint controls.
- DNA damage — for example, double-strand breaks. If repair is impossible, the accumulation of p53 protein initiates apoptosis via activation of Bax and Bak.
- Chromosome segregation errors — incorrect distribution of genetic material in the previous division.
- Mitotic apparatus defects — improper microtubule system structure or incorrect assembly of the mitotic spindle, checked during metaphase.
This mechanism serves as protection against the accumulation of mutations and prevents malignant transformation.
Class and exam questions
How does mitosis differ from meiosis in terms of DNA?
During mitosis, DNA doubles and the cell divides once, maintaining the diploid set (2n). During meiosis, after DNA duplication, two consecutive divisions occur (the second without replication), yielding a haploid set (n).
What is the restriction point?
This is the point at the end of the $G_1$ period. If a cell passes it, it is obligated to complete the cell cycle (enter the S phase) even if stimulating signals (mitogens) disappear.
Does all DNA double in the S phase?
No, centromeric regions are not replicated in the S phase. They duplicate later, at the beginning of mitotic anaphase, to hold sister chromatids together until that moment.
What else to study on this topic
- Mechanisms of DNA replication in the S phase
- Role of mitogens and cell cycle regulation
- Differentiation processes using epidermal cells as an example
- Life cycle and aging of long-lived postmitotic cells
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