The Cell Cycle: Structure, Function, and Regulation

Cell Cycle Overview

Introduction to the Cell Cycle

The cell cycle is the series of events that cells go through as they grow and divide. This process is fundamental for the reproduction of cells, organismal growth, and tissue repair. The cell cycle begins with the formation of a cell and ends with its division into two daughter cells.

• Key Functions: Reproduction of cells, growth, and tissue repair.

• Phases: Alternates between interphase (growth and DNA replication) and mitotic phase (division).

Organization of DNA

DNA Packaging and Chromosome Structure

Before cell division, DNA must be efficiently packaged. This organization is crucial for accurate segregation during cell division.

• Histones: Proteins around which DNA wraps to form nucleosomes.

• Chromatin: Strings of nucleosomes; non-condensed during most of the cell cycle.

• After DNA replication, chromatin condenses to form chromosomes, which are densely packed for division.

• Each replicated chromosome consists of two sister chromatids joined at a centromere.

• Kinetochore: Protein complex at the centromere that attaches chromatids to the mitotic spindle.

Genome: All genetic information in a cell. Prokaryotes have a single circular DNA molecule; eukaryotes have multiple linear chromosomes. Each species has a characteristic chromosome number (e.g., humans: 46, chimps: 48, elephants: 56).

• Homologous chromosomes: Pairs (one from each parent) with the same length, centromere position, and gene loci.

Types of Cells

Somatic Cells vs. Gametes

• Somatic cells: Body cells, diploid (2n), divide by mitosis (humans: 2n = 46).

• Gametes: Reproductive cells (sperm/egg), haploid (n), divide by meiosis (humans: n = 23).

Note: This unit focuses on mitosis.

Phases of the Cell Cycle

Interphase

Interphase is the longest phase (about 90% of the cell cycle) and consists of three subphases:

• G1 (First Gap): Cell is metabolically active, grows, duplicates organelles. Non-dividing cells may enter G0 (quiescent state).

• S (Synthesis): DNA replication occurs; each chromosome forms two sister chromatids.

• G2 (Second Gap): Final growth and preparation for mitosis; protein synthesis and ATP production increase, centrosomes replicate.

M Phase (Mitosis and Cytokinesis)

• Mitosis: Division of the nucleus.

• Cytokinesis: Division of the cytoplasm.

• Results in two genetically identical diploid daughter cells.

Phases of Mitosis

1. Prophase

• Early Prophase: Chromosomes condense, nucleoli disappear, mitotic spindle forms, centrosomes move apart.

• Late Prophase (Prometaphase): Chromosomes condense further, nuclear envelope breaks down, spindle microtubules attach to kinetochores.

2. Metaphase

• Centrosomes at opposite poles, chromosomes align at the metaphase plate, microtubules attach to kinetochores.

3. Anaphase

• Sister chromatids separate and move to opposite poles as microtubules shorten; cell elongates.

4. Telophase and Cytokinesis

• Mitotic spindle breaks down, nuclear envelopes reform, nucleoli reappear, chromosomes decondense.

• Cytokinesis: In animals, a cleavage furrow forms; in plants, vesicles from the Golgi form a cell plate.

Tracking Chromosomes During Mitosis

Chromosome and chromatid numbers change during mitosis. For humans:

Phase (Mitosis)	# Chromosomes	# Chromatids
Prophase	46	92
Metaphase	46	92
Anaphase	92	92
Telophase	92	92
End of Mitosis (separated cells)	46	46

Additional info: During anaphase, sister chromatids are considered individual chromosomes, doubling the chromosome count until cytokinesis completes.

Regulation of the Cell Cycle

Checkpoints

The cell cycle is regulated by checkpoints that ensure proper division:

• G1 Checkpoint: At G1/S transition; checks for cell size, growth factors, DNA damage. "Go" signal allows cycle to proceed; "Stop" sends cell to G0.

• G2 Checkpoint: At G2/M transition; checks for DNA replication completion and damage. "Stop" triggers repair or apoptosis if irreparable.

• M (Spindle) Checkpoint: At metaphase/anaphase transition; ensures all chromosomes are attached to spindle microtubules before separation.

Internal Cell Cycle Regulators

• Cyclins: Regulatory proteins whose concentrations fluctuate during the cell cycle.

• Cyclin-dependent kinases (CDKs): Enzymes that are active only when bound to cyclins; phosphorylate target proteins to drive cell cycle progression.

• Full activation of CDKs often requires phosphorylation by a Cyclin-Activating Kinase (CAK).

External Cell Cycle Regulators

• Growth factors: Hormones that stimulate cell division via signal transduction pathways.

• Contact inhibition: Cells stop dividing when they contact other cells.

• Anchorage dependence: Cells require attachment to a substrate to divide.

Cancer and the Cell Cycle

Loss of Cell Cycle Control

• Cancer arises from mutations in genes regulating the cell cycle.

• Cancer cells ignore checkpoints, divide uncontrollably, and evade apoptosis.

• Benign tumors: Abnormal cells remain at the original site.

• Malignant tumors: Cells invade other tissues (metastasis).

Cancer Prevention

• Avoid tobacco products; carcinogens cause DNA mutations.

• Eat a healthy diet and stay hydrated.

• Protect skin from UV radiation.

• Know family history and get regular screenings.

Practice Questions

• Example Multiple Choice: Movement of chromosomes during anaphase would be most affected by a drug that prevents shortening of microtubules.

• Example FRQ: If a cell has 50 chromosomes and after division one daughter cell has 49 and the other 51, this could be due to improper attachment of spindle fibers, leading to nondisjunction.