Chapter 11 - Nucleic Acids, DNA Replication, and Chromosomes

Introduction

• Focus on DNA structure and function, with a later discussion on RNA structure.
• DNA replication is crucial for cell division and reproduction.
• Overview of chromosome structure and organization in prokaryotic and eukaryotic cells.

Part 1 - Nucleic Acid Structure

• Structure-Function Relationship: Core concept in biology illustrated by DNA and RNA.
• Nucleic acid structure is essential for storing, replicating, and transmitting genetic information.
• Variations in DNA/RNA can occur through mutations, forming the genetic basis for evolution.

DNA Structure

• Levels of Complexity:
  • Nucleotides: Building blocks of nucleic acids.
  • DNA strands: Formed by covalent linkage of nucleotides.
  • Double Helix: Two antiparallel strands.
  • Chromatin: DNA and proteins for packaging in the nucleus.
  • Genome: Total genetic material in a cell (nuclear & organelle chromosomes).

Nucleotides

• Components:
  • Phosphate: Forms the DNA/RNA backbone.
  • Pentose Sugar: Ribose in RNA, deoxyribose in DNA.
  • Nitrogenous Bases:
  • Purines (double ring): Adenine (A), Guanine (G).
  • Pyrimidines (single ring): Thymine (T), Uracil (U), Cytosine (C).
• Orientation: Positions of carbon atoms are critical for nucleotide structure (1’, 2’, 3’, 4’, 5’).

DNA Strand Features

• Backbone Formation: Phosphodiester bonds connect nucleotides.
• Directionality: 5’ end has phosphate, 3’ end has -OH.
• Base Sequence: Determines genetic information storage; directionality is crucial (5’ - 3’ orientation).

DNA Double Helix

• Base Pairing: A always pairs with T, G with C; essential for the molecule’s width.
• Antiparallel Orientation: One strand (5’-3’), the other (3’-5’).
• Grooves: Major and minor grooves important for replication and gene expression.

Part 2 - DNA Replication Overview

• Replication uses a complementary model, with each parent strand acting as a template to form new strands.
• Semiconservative Mechanism: Each new DNA molecule has one parent and one daughter strand.

Steps of DNA Replication

1. Separation of Parent Strands: Breaks hydrogen bonds.
2. Base Pairing Rules: Enforced during the synthesis of daughter strands.
3. DNA Polymerases: Key enzyme involved in building new strands; processivity varies between leading and lagging strands.

Origin of Replication (ori)

• Definition: Starting point where replication begins; can be single in prokaryotes, many in eukaryotes.
• Replication Fork: Area of active enzymatic activity during replication.

DNA Replication Mechanics

• DNA Helicase: Unwinds the double helix by breaking hydrogen bonds.
• Topoisomerases: Prevent supercoiling ahead of the fork.
• Single-Stranded Binding Proteins: Stabilize separated DNA strands.

New Strand Synthesis

• Role of DNA Polymerases: Synthesize complementary strands based on parent strand.
• RNA primers are initiated by DNA primase to start synthesis.
• Leading vs. Lagging Strand: Continuous on leading strand, fragmented on lagging strand (Okazaki fragments).

Enzymes in Replication

• Common Names and Functions:
  • DNA Helicase: Separates strands.
  • Single-Strand Binding Protein: Stabilizes separated strands.
  • Topoisomerase: Alleviates tension ahead of the fork.
  • DNA Primase: Synthesizes RNA primers.
  • DNA Polymerase: Synthesizes DNA, proofreads.
  • DNA Ligase: Joins Okazaki fragments.

Accuracy of DNA Replication

• Errors are rare (1 mistake per 100 million nucleotides).
• High fidelity due to bonding specificity and proofreading abilities of DNA polymerases.

Part 4 - Telomeres and Telomerase

• Telomeres: Protect chromosomes; consist of non-coding repeated DNA sequences at chromosome ends.
• Problem of Shortening: Lagging strand synthesis leaves an overhang that cannot be fully replicated.
• Telomerase: Enzyme that extends telomeres, preventing shortening; often upregulated in cancers.

Part 5 - Molecular Structure of Eukaryotic Chromosomes

• Structure: Comprised of multiple linear chromosomes; humans have 23 pairs.
• Nucleosomes: DNA wrapped around histones, forming chromatin.
• 30 nm Fiber: Further compaction of nucleosomes.
• Radial Loop Domains: Structures anchoring to the nuclear matrix, leading to compaction.

Chromosomes and Compaction

• Chromosomes occupy distinct locations in the nucleus, determined by interactions with the nuclear lamina.
• Maximum compaction occurs during cell division, leading to recognizable X-shaped chromosomes.