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.