Cell Cycle and Mitosis

Overview of the Cell Cycle

The cell cycle is the series of events that cells undergo to grow and divide. It consists of several distinct phases, each with specific functions and checkpoints to ensure proper division.

• G1 phase: Cell growth and synthesis of proteins required for DNA replication.

• S phase: DNA replication occurs, producing sister chromatids.

• G2 phase: Preparation for mitosis, including synthesis of proteins for cell division.

• M phase: Mitosis (nuclear division) followed by cytokinesis (cytoplasmic division).

• G0 phase: Cells exit the cycle and do not divide (quiescent state).

• Checkpoints: Regulatory points that determine if the cell can proceed; cancer cells often bypass these.

Mitosis: Steps and Purpose

Mitosis is the process by which a cell divides its nucleus, resulting in two genetically identical daughter cells. It is essential for growth, repair, and asexual reproduction.

• Prophase: Chromosomes condense, spindle apparatus forms.

• Prometaphase: Nuclear envelope breaks down, spindle fibers attach to kinetochores.

• Metaphase: Chromosomes align at the metaphase plate.

• Anaphase: Sister chromatids separate and move to opposite poles.

• Telophase: Chromosomes decondense, nuclear envelope reforms.

• Cytokinesis: Division of the cytoplasm, completing cell division.

Counting Chromosomes: The number of centromeres equals the number of chromosomes. DNA replication doubles the DNA content but does not change chromosome number or ploidy.

• Humans: 2n = 46 chromosomes (diploid), n = 23 (haploid).

• Homologous chromosomes: One maternal and one paternal chromosome with the same genes but possibly different alleles.

• Sister chromatids: Identical copies formed during S phase.

Meiosis and Genetic Variation

Meiosis: Process and Outcomes

Meiosis is a specialized cell division that reduces chromosome number by half, producing four unique haploid gametes. It consists of one round of DNA replication followed by two divisions.

• Meiosis I: Homologous chromosomes pair (synapsis), cross over (prophase I), align as tetrads (metaphase I), and separate (anaphase I). Result: cells are haploid but chromosomes are still replicated.

• Meiosis II: No DNA replication; sister chromatids separate, similar to mitosis but in haploid cells.

• Outcome: Four unique haploid cells (gametes).

DNA Content vs. Ploidy: DNA doubles in S phase, halves after meiosis I, halves again after meiosis II. Each gamete has one copy of every gene.

Sources of Genetic Variation

• Crossing Over: Exchange of genetic material between non-sister chromatids during prophase I.

• Independent Assortment: Random orientation of homologous pairs during metaphase I.

• Random Fertilization: Any sperm can fertilize any egg, increasing genetic diversity.

• Mutation: Additional source of variation.

Gamete Diversity: Number of possible gametes from independent assortment is , where n is the number of homologous pairs.

• Example: For humans, million possible gametes.

Errors in Meiosis

• Nondisjunction: Failure of homologs or sister chromatids to separate, leading to aneuploidy (e.g., trisomy 21).

Mitosis vs. Meiosis

• Mitosis: Occurs in somatic cells; produces two identical diploid cells.

• Meiosis: Occurs in gonads; produces four unique haploid gametes.

• Homologs separate only in meiosis I.

• Crossing over and independent assortment occur only in meiosis I.

Mendelian Genetics and Pedigrees

Key Terms and Concepts

• Gene: DNA segment encoding an RNA or protein.

• Allele: Variant form of a gene.

• Genotype: Genetic makeup (e.g., AA, Aa, aa).

• Phenotype: Observable traits.

• Homozygous: Two identical alleles (AA or aa).

• Heterozygous: Two different alleles (Aa).

• Dominant allele: Expressed in heterozygotes.

• Recessive allele: Expressed only in homozygotes.

• Carrier: Heterozygote for a recessive disorder (Aa).

Mendel's Laws

• Law of Segregation: Alleles separate during anaphase I; each gamete receives one allele.

• Law of Independent Assortment: Genes on different chromosomes assort independently.

Genetic Ratios and Probability

• Monohybrid cross (Aa × Aa): Genotype ratio 1:2:1; phenotype ratio 3:1.

• Dihybrid cross (AaBb × AaBb): Phenotype ratio 9:3:3:1.

• Test cross: Crossing unknown dominant with homozygous recessive (aa) reveals genotype.

• Probability: Use multiplication for independent events (AND rule).

• Conditional probability: Adjust based on known outcomes (e.g., unaffected child of carriers).

Pedigree Analysis

• Symbols: Squares = males, circles = females, filled = affected.

• Recessive inheritance: Two unaffected parents with an affected child.

• Genotype deduction: Use phenotypes and offspring to infer genotypes.

Nucleic Acids and DNA Replication

Nucleotide Structure

• Nucleotide: Phosphate (5′C), sugar, base (1′C).

• RNA: Ribose sugar (OH on 2′C), bases A U G C, single-stranded.

• DNA: Deoxyribose (H on 2′C), bases A T G C, double-stranded.

• Purines: Adenine (A), Guanine (G).

• Pyrimidines: Cytosine (C), Uracil (U), Thymine (T).

• Base pairing: A=T (2 H bonds), G≡C (3 H bonds); %A = %T, %G = %C.

DNA Structure and Replication

• Antiparallel strands: 5′ to 3′ and 3′ to 5′ orientation.

• Phosphodiester bonds: Link nucleotides (3′ OH to 5′ phosphate).

• Replication direction: Chains grow 5′ → 3′ only.

• Semi-conservative replication: Each new DNA molecule contains one old and one new strand.

DNA Replication Steps

• Initiator proteins bind origin of replication.

• Helicase unwinds DNA, forming replication fork.

• Primase synthesizes RNA primer.

• DNA polymerase extends DNA 5′ → 3′ from primer, reads template 3′ → 5′, proofreads.

• Primer replaced with DNA.

• Ligase seals nicks in the sugar-phosphate backbone.

• Leading strand: Synthesized continuously.

• Lagging strand: Synthesized discontinuously as Okazaki fragments.

• Eukaryotes: Multiple origins of replication; replication bubbles.

Transcription, RNA Processing, and Translation

Central Dogma of Molecular Biology

The central dogma describes the flow of genetic information: DNA is transcribed into RNA, which is translated into protein. All cells have the same DNA, but gene expression varies by cell type.

Transcription

• Transcription factors bind promoter regions, recruit RNA polymerase.

• RNA polymerase synthesizes RNA 5′ → 3′, reads template 3′ → 5′ (no primer needed).

• RNA is complementary and antiparallel to the template strand; matches coding strand (U for T).

• Transcription ends at terminator sequence.

Eukaryotic mRNA Processing

• 5′ cap: Stability, export, ribosome recruitment.

• Poly-A tail: Stability, translation efficiency.

• Splicing: Removal of introns, joining of exons; alternative splicing allows multiple proteins from one gene.

Translation

• Ribosome reads mRNA 5′ → 3′ in codons (three nucleotides).

• 64 codons encode 20 amino acids (redundant code).

• Start codon: AUG (Methionine).

• Stop codons: UAA, UAG, UGA.

• Aminoacyl-tRNA synthetases charge tRNAs with correct amino acids.

• Anticodon on tRNA pairs antiparallel with codon on mRNA.

• Ribosome sites: A (aminoacyl), P (peptidyl), E (exit).

• Translation steps: Initiation → elongation (peptide bond formation, ribosome translocation) → termination (release factor binds stop codon).

Practice Questions and Answers

Sample Questions

• Identify cell cycle stages, meiosis events, and chromosome counting.

• Calculate gamete diversity, genotype and phenotype ratios, and probabilities in genetic crosses.

• Analyze DNA and RNA sequences, identify template and coding strands, and predict polypeptides.

• Draw and label mitosis and meiosis stages, track ploidy changes, and explain independent assortment.

Sample Answers

• Metaphase II is when a 2n = 4 cell has homologs lined up in a single column.

• Meiotic cell becomes haploid after meiosis I; homologs separate in meiosis I, sisters in meiosis II.

• For 2n = 6, independent assortment yields gametes.

• Aa × aa cross: genotype ratio 1:1 (Aa:aa), phenotype ratio 1:1; test cross with aa reveals genotype.

• Probability calculations: carriers of cystic fibrosis (autosomal recessive) have 1/4 affected child, 1/8 affected and male, 1/3 unaffected son is homozygous, 1/4 for two children both carriers.

• DNA sample with 16% adenine: 16% thymine, 34% guanine, 34% cytosine.

• Order of replication steps: proteins bind origin, helicase, primase, DNA polymerase, proofreading, ligase.

• DNA polymerase replaces RNA primer; ligase seals nicks.

• mRNA sequence: first three codons read by ribosome are AUG (Met), CCU (Pro), AAC (Asn).

• tRNA anticodon 3′-CGU-5′ pairs with codon 5′-GCA-3′, which codes for alanine (Ala).

• Transcription: template strand is the one RNA is made from, coding strand matches RNA (except U for T).

• Mitosis produces two AaBb (2n = 4) daughters; meiosis produces gametes AB, AB, ab, ab. Flipping B/b pair at metaphase I gives Ab, Ab, aB, aB (independent assortment).

• Ploidy: 2n = 4 at prophase I, n = 2 after meiosis I, n = 2 in gametes. Flipped orientation shows independent assortment.

Table: Comparison of Mitosis and Meiosis

Table: DNA vs. RNA

Key Equations and Concepts

• Gamete diversity: (n = number of homologous pairs)

• Base pairing: %A = %T, %G = %C

• Probability (AND rule):

Example: For a dihybrid cross AaBb × AaBb, probability of daughter that is aaB_ is .

Additional info: These notes expand on brief points from the review sheet, providing definitions, examples, and tables for clarity. Practice questions and answers are included to reinforce understanding of cell division, genetics, and molecular biology.