The Cell Cycle

Introduction to the Cell Cycle

The cell cycle is a fundamental process by which cells replicate and divide, ensuring growth, development, and maintenance of all living organisms. It consists of a series of phases that prepare the cell for division and ensure accurate transmission of genetic material.

• Cell division is the process by which new cells are formed from pre-existing cells.

• Organisms start life as single-celled embryos and grow through repeated cell divisions.

• Meiosis produces reproductive cells (gametes), while mitosis produces somatic cells (all other cell types).

Cellular Replication: Basic Steps

For life to persist, cells must replicate through a series of coordinated steps:

• Copying DNA: The cell duplicates its genetic material.

• Separating copies: The duplicated DNA is separated into two sets.

• Dividing cytoplasm: The cell splits its cytoplasm to form two complete cells.

Chromosome Structure and Function

What Is a Chromosome?

Chromosomes are the carriers of genetic information in cells. They consist of a single long double helix of DNA wrapped around proteins called histones.

• Gene: A region of DNA in a chromosome that codes for a specific RNA and, consequently, a specific protein.

• Before mitosis, chromosomes are replicated and condense into compact structures.

• Each double-stranded DNA copy is called a chromatid.

• Chromatids are attached by proteins called cohesions and, once mitosis begins, only at the centromere.

• Sister chromatids: Chromatid copies that remain attached at the centromere; two attached sister chromatids are considered a single chromosome.

Phases of the Cell Cycle

Alternation between M Phase and Interphase

Eukaryotic cells alternate between a dividing phase (M phase) and a non-dividing phase (interphase).

• M phase: Cells separate their chromosomes.

• Interphase: Chromosomes are uncoiled; cells grow, prepare to divide, or fulfill specialized functions.

• Cells spend most of their time in interphase.

The Discovery of S Phase and Gap Phases

Chromosome replication occurs only during interphase, specifically in the S (synthesis) phase. The cell cycle includes two gap phases (G1 and G2) where no DNA synthesis occurs.

• S phase: DNA replication occurs.

• G1 phase: Gap before S phase; cell grows and prepares for DNA replication.

• G2 phase: Gap after S phase; cell prepares for mitosis.

The Four Phases of the Cell Cycle

The cell cycle consists of four main phases:

• M phase (mitosis and cytokinesis)

• G1 phase (first gap)

• S phase (synthesis)

• G2 phase (second gap)

M Phase: Mitosis and Cytokinesis

Overview of M Phase

M phase consists of mitosis (division of replicated chromosomes) and cytokinesis (division of cytoplasm).

• Mitosis: Forms two daughter nuclei with identical chromosome genes.

• Cytokinesis: Forms two daughter cells by dividing the cytoplasm.

Chromatin and Chromosome Replication

Eukaryotic chromosomes are composed of DNA wrapped around histone proteins, forming chromatin. Chromatin is relaxed during interphase and condenses during mitosis.

• Each chromosome consists of two sister chromatids after S phase.

• Chromatids are exact copies of the same genetic information.

Events in Mitosis

Mitosis is a continuous process divided into five subphases:

• Prophase: Chromosomes condense; spindle apparatus forms.

• Prometaphase: Nuclear envelope breaks down; microtubules attach to chromosomes at kinetochores.

• Metaphase: Chromosomes align on the metaphase plate; spindle is fully formed.

• Anaphase: Sister chromatids are pulled apart toward opposite poles.

• Telophase: New nuclear envelope forms; chromosomes decondense.

Mechanisms of Chromosome Movement

During anaphase, kinetochore microtubules shorten, pulling chromatids apart. Motor proteins and microtubule dynamics drive chromosome movement.

• Kinetochore microtubules remain stationary but shorten as tubulin subunits are lost from their plus ends.

• Proteins from the kinetochore attach to a ring that moves along the microtubule as it disassembles.

Cytokinesis

Cytokinesis results in two daughter cells, with mechanisms varying between plants and animals.

• Plants: Vesicles from the Golgi apparatus fuse to form a cell plate.

• Animals: A ring of actin and myosin filaments contracts, forming a cleavage furrow.

Bacterial Cell Replication

Bacteria divide by binary fission, a process similar to eukaryotic M phase but without mitosis.

• Bacterial chromosomes are replicated.

• Protein filaments pull chromosomes apart; other proteins divide the cytoplasm.

Regulation of the Cell Cycle

Cell-Cycle Regulatory Molecules

Cell-cycle length varies among cell types and is regulated by specific molecules. The discovery of M-phase-promoting factor (MPF) revealed the importance of regulatory proteins.

• MPF is composed of a protein kinase and a cyclin subunit.

• MPF activity increases only after cyclin protein is translated.

• MPF protein kinase is a cyclin-dependent kinase (Cdk), active only when bound to cyclin.

Activation and Deactivation of MPF

MPF is regulated by phosphorylation and negative feedback mechanisms.

• MPF's Cdk subunit has two phosphorylation sites; removal of one phosphate activates the kinase.

• Deactivation occurs via negative feedback and destruction of cyclin by enzyme complexes.

Cell-Cycle Checkpoints

Cell-cycle checkpoints are critical points where regulatory molecules determine whether the cell proceeds with division.

• G1 checkpoint: Assesses cell size, nutrient availability, social signals, and DNA damage.

• G2 checkpoint: Ensures proper chromosome replication and DNA integrity.

• M-phase checkpoints: Ensure proper attachment and separation of chromosomes.

Cancer and Loss of Cell-Cycle Control

Cancer: Out-of-Control Cell Division

Cancer is a complex family of diseases caused by uncontrolled cell division due to failed cell-cycle checkpoints.

• Cancerous cells divide uncontrollably, invade tissues, and can spread (metastasis).

• Defects in cell division include activation of growth proteins and failure of tumor suppressor genes.

Properties of Cancer Cells

• Malignant tumors: Cancerous, invasive, and capable of metastasis.

• Benign tumors: Noncancerous and noninvasive.

Social Control and Cell-Cycle Checkpoints

Normal cells respond to growth factors and social signals, dividing only when beneficial. Cancer cells often divide without these signals.

• Growth factors stimulate production of regulatory proteins (e.g., E2F).

• Rb protein acts as a gatekeeper, inhibiting E2F and preventing S phase entry.

• Activated cyclin-Cdk dimer phosphorylates Rb, releasing E2F and allowing S phase entry.

Failure of Social Controls and Checkpoints

Cancer can result from overproduction of cyclin or defective Rb protein, leading to uncontrolled cell division.

• Overproduced cyclin permanently activates Cdk, continuously phosphorylating Rb.

• Defective Rb fails to bind E2F, allowing unregulated S phase entry.

Structures Involved in Mitosis

Table: Structures and Functions in Mitosis

The following table summarizes key structures involved in mitosis and their functions:

Key Terms and Concepts

• Apoptosis: Programmed cell death, often initiated by p53 protein in response to DNA damage.

• Metaphase plate: Imaginary plane where chromosomes align during metaphase.

• Metastasis: Spread of cancer cells to new locations in the body.

• Binary fission: Method of bacterial cell division.

Equations and Formulas

Cell cycle regulation involves phosphorylation reactions:

• Protein kinase reaction:

MPF activation and deactivation:

• MPF (Cyclin-Cdk) activation:

• MPF deactivation:

*Additional info: Academic context was added to clarify the phases, regulatory mechanisms, and cancer-related defects, as well as to reconstruct the table of mitosis structures and functions.*