BIOL 3510: Lecture 04
• DNA & Chromosomes
The structure of DNA
The structure of eukaryotic chromosomes
The regulation of chromosome structure
Nucleotides
• Nucleotides are
composed of a base,
sugar, and phosphate
group.
• Nucleotides are the
building blocks of the
nucleic acids.
• In deoxyribonucleic acid
(DNA), the sugar is
deoxyribose.
N-glycosidic
bond
H
H
H
H
H
Bases
• Bases are nitrogen-containing ring compounds,
either pyrimidines (C, T) or purines (A, G).
Phosphates
• The phosphates are normally joined to the C5 hydroxyl
of the sugar (designated 5’).
• Mono-, di-, and triphosphates are common.
• The phosphate makes a nucleotide negatively charged.
Nucleotides
• Nucleotides are linked together
by phosphodiester bonds to for
nucleic acids.
• Phosphodiester bonds form via
condensation reactions.
• Nucleotides can be purines (G, A)
or pyrimidines (T, C).
• DNA strands have a polarity
(5’→3’).
• DNA strands are negatively
charged.
DNA structure
OH
• A DNA molecule consists
of 2 complementary chains
of nucleotides in an antiparallel conformation
• The DNA strands are hold
together by hydrogen
bonds:
- 2 H-bonds between A & T
- 3 H-bonds between G & C
OH
DNA structure
• The 2 DNA strands
wind around each
other to form a double
helix.
• The double helix
contains 10 base pairs
(bp) per turn.
• The coiling creates
two grooves (one
major, and one minor)
BIOL 3510: Lecture 04
• DNA & Chromosomes
The structure of DNA
The structure of eukaryotic chromosomes
The regulation of chromosome structure
Chromosome structure
• A genome is all the information contained within an organism’s DNA.
• Eukaryotic DNA is divided into chromosomes.
• Homologous chromosomes are the pair of maternal and paternal
chromosomes.
• The karyotype is a display of mitotic chromosomes.
Chromosome structure
• Human Genome Project
produced the first draft
sequence of human
genome (2001).
• 22 autosomes and 2 sex
chromosomes.
• 3.2 billion base pairs.
• Approximately 30,000
genes.
• Only 1.5% of the genome is
exons (protein coding
regions).
Chromosome structure
• The duplication and segregation of chromosomes occurs through
the cell cycle:
- The interphase, when chromosomes are duplicated.
- The mitosis, when chromosomes are distributed to the 2 daughter
cells.
Chromosome structure
• Three DNA sequence elements ensure chromosome can be
replicated and segregated at mitosis:
- The replication origin, where the replication of DNA begins.
- The telomeres, repeated nucleotide sequences at the end of
chromosomes.
- The centromere allows duplicated chromosomes to be separated.
Chromosome structure
• DNA in mitotic chromosomes is condensed.
• DNA in interphase chromosomes is less compact.
• Chromatin = DNA + Associated Proteins
Mitotic chromosome
Interphase chromatin
Chromosome structure
• Interphase chromosomes are contained within the nucleus of
eukaryotic cells.
• Nuclear envelope = 2 co-centric lipid bi-layers
• Nuclear pores allow exchange between the cytoplasm and nucleus.
• Nuclear lamina = mesh of intermediate filament that support the
nucleus.
Chromosome structure
Interphase chromosomes occupy their own distinct
territories within the nucleus.
Chromosome structure
• Nucleosomes are the basic units of chromatin
packing.
• A nucleosome consists of:
- 4 pairs of histones (octamer). Histones are
highly conserved, positively charged proteins.
- 147 bp piece of DNA
Chromosome structure
• Nucleosomes are further packed into 30 nm fibers via:
- Covalent chemical modifications of the histone tails of the
nucleosome core particles
- A linker histone H1 pulls nucleosomes together and pack them
into a more compact chromatin fiber.
Interphase chromatin
Chromatin experimentally unpacked
“bead-on-a-string”
Chromosome structure
• DNA packing occurs on several levels in chromosomes.
Mitotic chromosome with tightly
packed chromatin.
BIOL 3510: Lecture 04
• DNA & Chromosomes
The structure of DNA
The structure of eukaryotic chromosomes
The regulation of chromosome structure
Regulation of chromosome structure
• Changes in nucleosome structure allow access to DNA.
• Chromatin-remodeling complexes slide DNA on nucleosomes in an
ATP dependent manner, making it accessible to other DNA-binding
proteins.
Regulation of chromosome structure
• Each histone tail can be modified by covalent attachment of
chemical groups (methylation, phosphorylation, acetylation,
ubiquitylation)
• Covalent chemical modification of the histone tails:
- disrupt the stability of the 30
nm fibers and higher order
packing
- recruits proteins that
condense of decondense
chromatin
Regulation of chromosome structure
• The pattern of histone modification indicates the status of the
nearby chromatin.
Regulation of chromosome structure
There are 2 main levels of interphase chromatin condensation:
• Heterochromatin:
- Most condensed
- Induced by tail modifications, including methylation of Lys 9
on the histone H3 tail
- Gene poor regions (centromeres and telomeres)
- Genes are not expressed
• Euchromatin:
- Less condensed
- Gene rich region
Regulation of chromosome structure
Heterochromatin-specific modifications allow heterochromatin
to form and spread.
Regulation of chromosome structure
Example of heterochromatin formation: inactivation of one of
the 2 X chromosomes in the cells of mammalian females.