Cell Division and Protein Synthesis: Study Notes for Anatomy & Physiology

Cell Cycle

Overview of the Cell Cycle

The cell cycle is a series of changes a cell undergoes from the time it is formed until it reproduces. It consists of two major periods:

• Interphase: The cell grows and carries on its usual activities.

• M (Mitotic) Phase: The cell divides into two daughter cells.

Cells not actively dividing are in the G0 phase.

Interphase

Subphases of Interphase

Interphase is the period from cell formation to cell division, during which the cell carries out routine activities and prepares for division. Nuclear material is in the uncondensed chromatin state.

• G1 (Gap 1): Vigorous growth and metabolism. Cells that permanently cease dividing are said to be in G0 phase.

• S (Synthetic): DNA replication occurs.

• G2 (Gap 2): Preparation for division.

S Phase: DNA Replication

Mechanism of DNA Replication

• Double-stranded DNA helices unwind and unzip.

• Replication fork: Point where strands separate; replication bubble: Active area of replication.

• Each strand acts as a template for a new complementary strand.

• RNA starts replication by laying down a short strand that acts as a primer.

• DNA polymerase attaches to primer and adds complementary nucleotides to form new strand. Leading strand is synthesized continuously; lagging strand is synthesized discontinuously (Okazaki fragments).

• DNA ligase splices short segments of lagging strand together.

DNA Replication (cont.)

• End result: Two identical "daughter" DNA molecules are formed from the original.

• During mitotic cell division, one complete copy is given to each of the two resulting daughter cells.

• Histone proteins are incorporated as DNA is synthesized.

• This process is called semiconservative replication because each double-stranded DNA is composed of one old strand and one new strand.

Cell Division

Overview

Most cells replicate continuously for growth and repair. Skeletal, cardiac, and nerve cells do not divide efficiently; damaged cells are replaced with scar tissue.

• M (Mitotic) Phase consists of two events:

  1. Mitosis (nuclear division):

     • Prophase

     • Metaphase

     • Anaphase

     • Telophase

  2. Cytokinesis (division of cytoplasm)

Control of cell division is crucial to prevent unnecessary division.

Mitosis: Phases

Prophase

• Early Prophase: Chromatin condenses into visible chromosomes. Each chromosome and its duplicate (sister chromatids) are held together by a centromere. Centrosomes begin synthesizing microtubules (mitotic spindle).

• Late Prophase: Nuclear envelope breaks up. Microtubules attach to kinetochores and pull chromosomes to the cell's equator. Non-kinetochore microtubules push against each other, moving poles apart.

Metaphase

• Centromeres of chromosomes are aligned at the cell's equator (metaphase plate).

Anaphase

• Shortest phase. Centromeres split, separating sister chromatids.

• Chromatids are pulled toward opposite poles by motor proteins of kinetochores.

Telophase

• Chromosome movement stops. Chromosomes uncoil to form chromatin.

• New nuclear membranes form, nucleoli reappear, spindle disappears.

• Cytokinesis begins during late anaphase and continues through mitosis. Actin microfilaments form a cleavage furrow, pinching the cell into two daughter cells.

Control of Cell Division

Regulation Mechanisms

• "Go" signals: Critical surface-to-volume ratio, chemicals (growth factors, hormones).

• "Stop" signals: Availability of space; contact inhibition (cells stop dividing when they touch other cells).

• Key proteins: Cyclins (regulatory proteins) and Cdks (cyclin-dependent kinases) activate cell division.

• Checkpoints: Ensure cell division processes are correct; G1 checkpoint is the most important.

Protein Synthesis

Genetic Code and Genes

• DNA is the master blueprint for protein synthesis, directing the order of amino acids in a polypeptide.

• A gene is a segment of DNA that codes for a polypeptide.

• The code is determined by the order of nitrogen bases (Adenine, Guanine, Thymine, Cytosine).

• Code consists of three sequential bases (triplet code). Each triplet specifies a particular amino acid.

• Genes are composed of exons (expressed) and introns (removed during processing).

Steps of Protein Synthesis

• Transcription: DNA information is coded into mRNA.

• Translation: mRNA is decoded to assemble polypeptides.

The Role of RNA

• RNA is the "go-between" molecule linking DNA to proteins.

• RNA copies the DNA code in the nucleus and carries it to ribosomes in the cytoplasm.

• RNA differs from DNA: Uracil replaces thymine; ribose replaces deoxyribose.

• Three types of RNA:

  1. Messenger RNA (mRNA)

  2. Ribosomal RNA (rRNA)

  3. Transfer RNA (tRNA)

The Types of RNA

• mRNA: Single-stranded; carries code from DNA to ribosome.

• rRNA: Structural component of ribosomes; helps translate mRNA into polypeptide.

• tRNA: Carrier of amino acids; contains anticodon that pairs with mRNA codon during translation.

Transcription

Process and Phases

• Transcription factors activate transcription by loosening histones and binding to the promoter region of the gene.

• RNA polymerase synthesizes mRNA from the DNA template strand.

Phases of Transcription

1. Initiation: RNA polymerase separates DNA strands.

2. Elongation: RNA polymerase adds complementary nucleotides to the growing mRNA strand. A short DNA-RNA hybrid is formed.

3. Termination: Transcription stops when RNA polymerase reaches a termination signal code.

Processing of mRNA

• Newly formed mRNA (pre-mRNA) is edited before translation.

• Introns are removed by spliceosomes, leaving only exon coding regions.

Genetic Code

• Each three-base sequence on DNA (triplet code) is represented by a complementary codon on mRNA.

• There are 64 possible codons (4 bases, 3 places: $4^3 = 64$).

• Three are stop codons; the rest code for amino acids.

• There are only 20 amino acids, so some amino acids are represented by more than one codon (redundancy protects against errors).

Translation: tRNA

• tRNA binds a specific amino acid at one end (aminoacyl-tRNA).

• Anticodon at the other end pairs with the complementary codon on mRNA.

• tRNA will only bind to codon on mRNA that is complementary.

The Steps of Translation

• Translation is the process of converting the language of nucleic acids into proteins.

• Involves mRNA, genetic code, tRNA, ribosomes, and translation events.

• Occurs in three phases:

  1. Initiation: Small ribosomal subunit binds to initiator tRNA (methionine) and mRNA. Ribosome scans for start codon (AUG).

  2. Elongation:

     • Codon recognition: tRNA binds complementary codon in A site.

     • Peptide bond formation: Ribosomal enzymes transfer and attach growing polypeptide chain from tRNA in P site to amino acid of tRNA in A site.

     • Translocation: Ribosome shifts down three bases, displacing tRNAs by one position.

  3. Termination: When a stop codon enters the A site, translation ends. Protein release factor binds, causing release of the polypeptide chain and separation of ribosome subunits.

• Polyribosomes (multiple ribosomes on one mRNA) produce multiple copies of the same protein.

Autophagy, Proteasomes, and Apoptosis

• Autophagy: Disposal of nonfunctional organelles and cytoplasmic bits by forming autophagosomes, which are degraded by lysosomes.

• Proteasomes: Disassemble ubiquitin-tagged proteins, recycling amino acids.

• Apoptosis: Programmed cell death; caspases degrade DNA and cytoskeleton, leading to cell death and phagocytosis by macrophages.

Cellular Growth and Development

• All cells contain the same DNA, but not all perform the same function (cell differentiation).

• Chemical signals in embryos channel cells into specific developmental pathways.

• Cell division in adults replaces short-lived cells and repairs wounds.

• Hyperplasia: Accelerated growth increasing cell numbers.

• Atrophy: Decrease in size due to loss of stimulation or use.

Cell Aging

• Wear and tear theory: Chemical insults and free radicals accumulate over time.

• Mitochondrial theory of aging: Free radicals in mitochondria diminish energy production.

• Immune system disorders: Autoimmune responses and weakened immunity.

• Genetic theory: Cessation of mitosis and cell aging are programmed into genes.

  • Telomeres (nucleotide strings) protect chromosome ends; shorten with each division.

  • Telomerase enzyme lengthens telomeres (present in germ cells and cancer cells).

  • Telomerase makes cancer cells immortal.

Clinical – Homeostatic Imbalance

• Progeria: Rare disease mimicking aging, caused by defective progerin protein in the nuclear lamina.

• Symptoms: Slow growth, thinning hair, brittle bones, arthritis, severe cardiovascular disease; death usually by age 20.

• Drug therapies that stimulate autophagy may help clear out progerin.

Discussion Questions

1. Explain why DNA replication is said to be "semiconservative".

2. Compare ribosomal and transfer RNA.

3. As you age, your body weakens and becomes less capable and more prone to injury. Why is this?