JC

lecture 4

Page 1

  • Title: DNA and Eucaryotic Chromosomes

Page 2

Structure of DNA

  • DNA: DeoxyriboNucleic Acid

  • "Backbone":

    • Composed of deoxyribose sugar molecules

    • Linked by phosphate groups via phosphodiester covalent bonds (which are polar)

Page 3

Properties of DNA

  • DNA is classified as an acid

  • At pH 7:

    • Hydrogen ions (Hδ+) from the phosphate groups are displaced by oxygen (Oδ-) from water molecules

Page 4

Ionization of Phosphate Groups

  • This results in the formation of hydronium ions (H3O+)

  • Consequently, most phosphate groups carry a negative charge at any given time

Page 5

Nitrogenous Bases in DNA

  • DNA contains four nitrogenous bases, each covalently bonded to sugar molecules:

    • Thymine (T)

    • Guanine (G)

    • Cytosine (C)

    • Adenine (A)

Page 6

Composition of Eucaryotic DNA

  • Result: Long polymer of deoxyribonucleotides, ranging from 50 to 300 million per mammalian chromosome

  • Types of deoxyribonucleotides:

    • Thymidine (Thymine)

    • Guanosine (Guanine)

    • Cytidine (Cytosine)

    • Adenosine (Adenine)

Page 7

Nucleosides and Nucleotides

  • Adenine (a nitrogenous base):

    • When attached to a 5-carbon sugar ring, it forms a nucleoside called adenosine

    • Examples:

      • Adenosine Monophosphate (AMP)

      • Adenosine Diphosphate (ADP)

      • Adenosine Triphosphate (ATP)

    • These are nucleotides made of base + sugar + one or more phosphates

    • Nucleotides in DNA are termed deoxyribonucleoside monophosphates

Page 8

Guanosine Triphosphate (GTP)

  • GTP: Guanosine Triphosphate, a nucleotide composed of:

    • Guanine base

    • Deoxyribose sugar

    • Three phosphate groups

  • Not on the test: Terminology of nucleoside and nucleotide

Page 9

DNA Structure

  • DNA consists of two "backbones" connected via hydrogen bonds between bases

  • Base pairing is complementary and arranged anti-parallel

  • Chemically different ends exist for each strand

Page 10

DNA Content in Eucaryotes vs Procaryotes

  • Procaryotes: Nearly 100% genome consists of mRNA, rRNA, and tRNA

  • Eucaryotes:

    • ~5% of genome consists of mRNA, rRNA, tRNA genes

    • ~80% dedicated to other RNA genes

    • Remaining 15% includes non-coding regulatory and non-regulatory regions

Page 11

Eucaryotic DNA Overview

  • Focus on structures and functions of eucaryotic DNA

Page 12

Segregation of Eucaryotic DNA

  • Eucaryotic DNA is separated from the cytoplasm by the nuclear envelope (nucleus)

  • This separation from cellular processes leads to significant implications, particularly in the organization of DNA

Page 13

Unique Features of Eucaryotic DNA

  • Eucaryotic cells possess DNA in the double helix form

  • Procaryotic cells generally have one circular DNA molecule lacking true chromosome architecture

  • Eucaryotic cells contain multiple linear DNA molecules, which are tightly packaged into chromosomes

    • Examples of organisms (e.g., ant vs. butterfly) show variation in chromosome numbers

Page 14

Chromosome Basics

  • Eucaryotic chromosomes are located in the nucleus

  • Each chromosome = one double-stranded DNA molecule during interphase

  • Following S-phase, chromosomes exist as two sister chromatids

Page 15

Eucaryotic Chromosome Overview

  • Examination of eucaryotic chromosomes and their organization

Page 16

Levels of Eukaryotic DNA Packaging

  • DNA exists in various packaging forms:

    • Short region of 2 nm double helix

    • 11 nm "beads-on-a-string" form of chromatin

    • 30-nm chromatin fiber consisting of packed nucleosomes

    • 300 nm condensed sections of chromosome

    • 700 nm section containing the centromere of a chromosome

    • Entire mitotic chromosome measures 1400 nm

Page 17

Nucleosome Composition

  • Nucleosomes consist of a complex of 8 proteins (histones)

  • DNA is wrapped twice around the histone complex and maintained by hydrogen bonds

Page 18

Chromatin Fiber Structure

  • Formed from folded strings of nucleosomes

  • Interactions between N-terminal tails of adjacent histone subunits help maintain structure

  • H1 and other non-histone DNA-binding proteins contribute to chromatin structure

Page 19

Chromatin Fiber Components

  • Structure includes sequence-specific DNA-binding proteins and nucleosomes

Page 20

Chromatin Control

  • Chromosomal structures vary across different regions:

    • Euchromatin: less condensed, ~90% of genes are present

    • Heterochromatin: highly condensed, includes centromeres and telomeres

  • Chromatin-remodeling complexes use ATP to drive modifications to histones, affecting gene expression

Page 21

Chromatin Variation

  • Euchromatin is more accessible for gene expression, while heterochromatin is often transcriptionally inactive and silenced

Page 22

Histone Tail Modifications

  • Modifications to histone tails can influence chromatin structure:

    • Acetylation: leads to loose packing

    • Methylation: causes tighter and various levels of condensation

    • Phosphorylation: increases condensation during cell division

Page 23

Additional Chromatin Variants

  • Variant histones provide further diversity to chromatin structure, synthesized during interphase

  • Inserted into existing structures, enhancing complexity

Page 24

The Histone "Code"

  • Modifications and insertions of histone variants create a histone code, which helps determine chromatin packaging and gene expression patterns

Page 25

Inheritance of Chromatin Structures

  • Some variable features of chromatin structures are inherited epigenetically, based on protein structure not DNA sequence

  • Chromatin structures play crucial roles in maintaining chromosome identities, with features absent in procaryotic DNA.