Cell cycle and life cycle of a cell
The cell cycle is the period of a cell's life from one division to another. It should not be confused with the life cycle, which spans the time from the birth of a cell to its death. Division itself (mitosis) accounts for only about 10% of the cell cycle, while the remaining 90% is occupied by interphase, the preparation for division.
In the body, different cells spend varying amounts of time in the cell cycle:
- Continuously dividing cells — for example, blood stem cells, which do not exit the cycle.
- Quiescent cells — for example, hepatocytes, which enter a resting state in the absence of liver damage, but return to the cycle in pathology (cirrhosis, regeneration).
- Terminally differentiated cells — for example, neurons, which have lost the ability to divide.
Structure of interphase
Interphase includes three consecutive periods:
- Presynthetic (G1) — the longest, up to several days.
- Synthetic (S) — about 5 hours.
- Postsynthetic (G2) — up to 8 hours.
The purpose of interphase is proper preparation for division and accurate transmission of genetic material to daughter cells.
Presynthetic period (G1)
Begins immediately after mitosis. The cell actively grows, restores organelles and cytoplasm volume, undergoes intensive metabolism, synthesis of proteins, lipids, and carbohydrates. The period concludes with preparation for DNA replication.
A key regulatory role is played by cyclin-dependent kinases (CDKs). These are enzymes that perform protein phosphorylation and are active only in a complex with regulatory proteins — cyclins (groups D, E, A, B). Cyclins are synthesized throughout the cycle and degraded at the onset of anaphase.
Effects of the cyclin–CDK complex:
- phosphorylation of nuclear envelope proteins and preparation for its disassembly;
- cytoskeleton remodeling;
- activation of DNA replication genes.
An example of CDK action is the regulation of the E2F transcription factor. In an inactive state, it is bound to the retinoblastoma protein (Rb). CDK, with the participation of ATP, phosphorylates Rb, releasing E2F, which activates the transcription of replication enzymes.
Restriction point and the role of the p53 protein
In each period of interphase, there is a restriction (checkpoint) point where DNA integrity is checked. When DNA is damaged, the P53 gene is activated, and a protein of the same name is synthesized, which:
- suppresses replication and stimulates DNA repair with the participation of DNA polymerases;
- activates the P21 and P27 genes, whose proteins inhibit CDKs and halt the cell cycle;
- if repair is impossible, directs the cell down the pathway of apoptosis.
After passing the restriction point, the cell transitions to the S-phase regardless of external signals. Mutations in P53 lead to cell division with DNA abnormalities and tumor formation. Dominant mutations of the retinoblastoma protein gene cause the development of retinoblastoma, because E2F remains permanently free and the cell continuously enters the cycle.
Synthetic period (S)
In the S-phase, the following occur:
- DNA replication;
- synthesis of histones required for chromatin condensation;
- duplication of the centrosome (cell center);
- second checkpoint — verification of replication accuracy and repeated repair.
Replication disorders are associated with pathologies such as Louis-Bar syndrome (ataxia-telangiectasia), accompanied by capillary dilations and coordination disorders, as well as xeroderma pigmentosum.
Postsynthetic period (G2) and MPF
In the G2 period, the following are carried out:
- synthesis of tubulins to build microtubules of the mitotic spindle;
- disassembly of centriolar satellites and formation of a halo at the cell center;
- post-replicative DNA repair;
- preparation for the disassembly of the Golgi apparatus and endoplasmic reticulum;
- synthesis of mitosis-promoting factor (MPF).
MPF exerts its effects only in prophase of mitosis:
- phosphorylation of lamin proteins and breakdown of the nuclear membrane;
- phosphorylation of histone H1 and chromosome condensation;
- phosphorylation of structural and contractile apparatus proteins and destruction of interphase microtubules to build mitotic spindle fibers.
Nuclear-to-cytoplasmic ratio across periods
Cell growth dynamics are reflected in the nuclear-to-cytoplasmic ratio:
- in G1, it is less than one — the cytoplasm grows predominantly, restoring volume after division;
- in S, it is greater than one — the nucleus actively enlarges due to DNA replication;
- in G2, the ratio equalizes and approaches one.
Key points
- The cell cycle spans from division to division; interphase takes up about 90% of its duration.
- Interphase consists of the G1 (presynthetic), S (synthetic), and G2 (postsynthetic) periods.
- Regulators of the cycle are cyclin–CDK complexes that phosphorylate key proteins.
- The E2F transcription factor is released from the complex with the Rb protein after its phosphorylation and triggers replication.
- At restriction points, the p53 protein monitors DNA integrity, activating repair or apoptosis via p21 and p27.
- Mutations in p53 lead to tumor growth; mutations in the Rb gene lead to retinoblastoma.
- In G2, MPF is synthesized, realizing its effects in mitotic prophase: nuclear envelope disassembly and chromosome condensation.
- The nuclear-to-cytoplasmic ratio changes predictably: <1 in G1, >1 in S, ≈1 in G2.