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BIO130: Genes and Cellular Functioning
DNA Structure and Function
- Deoxyribonucleic acid (DNA):
- Description: Long, thread-like molecule with a uniform diameter and varied length.
- Human Cells: Contains 46 DNA molecules (chromosomes) in the nucleus.
- Average Length: An average human DNA molecule is about 2 inches long.
DNA and Nucleic Acids Structure
- Nucleotides: DNA and other nucleic acids are polymers of nucleotides.
- Each nucleotide consists of three components:
- Sugar: Deoxyribose
- Phosphate Group
- Nitrogenous Base:
- DNA Bases: Adenine (A), Thymine (T), Cytosine (C), Guanine (G)
- Purines: Adenine (A), Guanine (G) - have double-ringed structure
- Pyrimidines: Cytosine (C), Thymine (T), Uracil (U) - have single-ringed structure.
The Genetic Code
- DNA Alphabet: A, T, C, G
- Triplets: Within a gene, groups of 3 nucleotides in the template strand of DNA form "words" known as triplets.
- Example triplets: ATG, GCG, TCA, GGT, CAT. There are 64 different possible combinations.
- Each triplet codes for a specific amino acid in the protein encoded by the gene.
- Gene containing 3,000 nucleotides (1,000 triplets) codes for a protein of 1,000 amino acids.
Structure of DNA
- Double Helix Shape: Resembles a spiral staircase.
- Backbones: Comprised of alternating phosphate groups and deoxyribose.
- Base Pairings: Step-like connections between backbones formed by nitrogenous bases united by hydrogen bonds:
- Purines pair with pyrimidines: A with T (connected by 2 hydrogen bonds), G with C (connected by 3 hydrogen bonds).
- Law of Complementary Base Pairing: Sequence of one strand governs the sequence of the other.
DNA Function
- Essential Function: DNA carries instructions (genes) for synthesizing proteins.
- Gene: A segment of DNA coding for the synthesis of a specific protein.
- Gene Count: Humans possess approximately 20,000 genes, constituting about 2% of total DNA while 98% is noncoding (plays roles in chromosome structure and regulating gene activity).
- Chromatin: Fine filamentous DNA material complexed with proteins known as histones, organized into 46 chromosomes in most cells.
Chromatin Structure
- Chromatin is dynamic within nondividing cells; structure and location change according to genetic activity.
- Genes can be turned on or off.
- During Cell Division: Cell duplicates all nuclear DNA, resulting in each chromosome consisting of two identical filaments called sister chromatids joined at a constricted centromere. Kinetochores are protein plaques on each side of the centromere that assist in cell division.
RNA Structure and Function
- Ribonucleic Acids (RNAs): Various forms and diverse functions.
- General structure includes sugar ribose with bases A, U, G, C (with uracil (U) replacing thymine).
- Primarily exists as a single nucleotide chain in the cytoplasm.
- Types of RNA important for protein synthesis:
- Messenger RNA (mRNA): Carry codes from the nucleus to the cytoplasm.
- Ribosomal RNA (rRNA): Forms part of ribosomal structure.
- Transfer RNA (tRNA): Delivers specific amino acids to ribosomes.
Definition of a Gene
- Gene: An information-containing segment of DNA coding for the production of an RNA molecule, often involved in synthesizing proteins.
- Each protein's amino acid sequence is determined by nucleotide sequences in DNA.
- Human chromosomes count: 46 chromosomes paired in sets of 23 from each parent, totaling 3.1 billion nucleotide pairs.
- Genomics: The study of the entire genome.
The Genetic Code and Protein Synthesis
- The human body can produce millions of different proteins from 20 amino acids encoded by genes made from 4 nucleotides (A, T, C, G).
- Genetic Code: Represents the system for encoding amino acid sequences using nucleotide triplets.
- Base Triplet: A sequence of three DNA nucleotides representing one amino acid.
- Codon: A three-base sequence in mRNA; there are 64 possible codons:
- 61 codons code for amino acids; 3 are stop codons.
- Start Codon: AUG coding for methionine initiates protein synthesis.
- Stop Codons: UAG, UGA, UAA signal the end of protein synthesis.
Protein Synthesis Overview
- All body cells (except sex cells and some immune cells) contain identical genes; however, different genes are activated in different cells.
- The process of protein synthesis follows:
- From DNA to RNA: Transcription processes to make mRNA from DNA.
- From RNA to Protein: Translation processes to synthesize a protein from mRNA.
- Transcription: The copying of genetic instructions from DNA to mRNA, utilizing the enzyme RNA polymerase to create a complementary RNA strand.
Translation of mRNA to Protein
- Translation Mechanism: Converts nucleotide language into amino acid language.
- Major Components Involved:
- mRNA: Carries genetic information from nucleus to cytoplasm.
- Contains a protein cap for ribosome recognition.
- tRNA: Delivers amino acids to the ribosome; contains an anticodon corresponding to the mRNA codon.
- Ribosomes: Read mRNA and build peptide chains with a large subunit and a small subunit, located free in cytosol or on rough ER.
- Three Sites in Ribosomes: E site, P site, and A site, all play roles during translation.
Steps of Translation
- Initiation: Ribosome assembles with mRNA in cytosol, binding starts at the leader sequence, initiating synthesis at the AUG start codon. tRNA brings methionine.
- Elongation: tRNA carrying amino acids binds at the A site; peptide bond formation between amino acids; ribosome shifts down codons, continuing elongation of the peptide chain.
- Termination: Ribosome reaches a stop codon, binding a release factor, resulting in ribosome disassembly and cessation of protein synthesis.
- Proteins destined for lysosomes or secretion are further modified by the ER and packaged into transport vesicles for delivery.
Protein Processing and Secretion
- Final Assembly: Proteins made in ribosomes in the cytoplasm later undergo the processing and secretion stages.
- Mechanism: Polyribosomes facilitate production efficiency.
Synthesis of Compounds Other Than Proteins
- Cells can synthesize compounds such as glycogen, fat, steroids, phospholipids, and pigments without having direct genes for them.
- These processes are regulated by enzymatic reactions, which are themselves encoded by genes.
- Example: Testosterone synthesis involves converting cholesterol within the testes, a process dependent on the activation of enzyme-related genes.
DNA Replication and Cell Cycle Overview
- Before cell division, DNA must replicate to ensure each daughter cell receives a complete set of genetic information.
- The process is highly accurate, relying on the law of complementary base pairing for prediction during replication.
DNA Replication Process
- Enzymatic Role: DNA Polymerase enzymes:
- Unwind the helical DNA.
- Break hydrogen bonds between complementary strands creating a replication fork.
- Read nucleotide sequences to synthesize new complementary strands from available free nucleotides.
- At the end of replication, each cell has 46 pairs of DNA molecules (totaling 96 single-stranded).
Semiconservative DNA Replication
- This replication method is called semiconservative because resulting DNA molecules consist of one original strand and one newly synthesized strand.
Errors and Mutations in DNA Replication
- DNA polymerase can make errors during replication.
- DNA Damage Response (DDR): Mechanisms exist to correct replication errors with a typical error rate of one mistake per billion bases.
- Mutations: structural changes in DNA caused by errors or environmental factors such as radiation or chemicals.
- They can lead to benign effects, cell death, cancer, or genetic defects over generations.
- Genetic Mosaicism: Variation within an individual’s genome due to mutations or replication errors.
The Cell Cycle
- The cell cycle includes interphase and the mitotic phase:
- Interphase Subphases:
- G1 (First Gap Phase): Normal cellular function, prepares for DNA replication.
- S (Synthesis Phase): DNA replication and centriole duplication.
- G2 (Second Gap Phase): Cell repairs, grows, and synthesizes enzymes for division.
- Mitotic Phase consists of:
- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis (cytoplasmic division occurs).
- G0 Phase: Describes cells that have exited the cell cycle and cease dividing for extended periods or permanently.
Mitosis Overview
- Mitosis: Cell division resulting in two genetically identical daughter cells.
- Key Functions:
- Development from fertilized egg to trillions of cells.
- Tissue growth, repair, and cell replacement post-birth.
- Four Phases of Mitosis:
- Prophase: Chromatin condenses into chromosomes, centrioles form spindle fibers, and the nuclear envelope disintegrates.
- Metaphase: Chromosomes align along the cell equator; spindle apparatus forms.
- Anaphase: Sister chromatids are separated and move to opposite cell poles.
- Telophase: Distinct nuclear envelopes form around each cluster of chromosomes; chromosomes decondense.
- Cytokinesis: Division of the cytoplasm that follows mitotic division, creating two separate daughter cells.
- Regulation of division relies on the presence of cytoplasmic volume, nutrient levels, presence of growth factors, and cell contact inhibition to halt divisions when not necessary.