Chapter 5: DNA and Chromosomes

Thursday, February 3, 2022

The structure of DNA

DNA: deoxyribonucleic acid: consists of 2
long polynucleotide chains
• Composed of 4 types of nucleotide subunits
(base + sugar phosphate backbone)
• Polynucleotide chains are held together by
hydrogen bonds between the nucleotides
DNA encodes genetic information of the cell
that is transmitted from generation to
generation

Nucleotide subunits within a DNA

strand are held together by
phosphodiester bonds
Sugar phosphate backbone is linked
together by phosphodiester bonds
Nucleotide base is connected to 1’
carbon of the sugar molecule
Phosphodiester bonds link the 5’
(prime) end of one sugar to the 3’ end
of the next

The two strands of the DNA double

helix are held together by hydrogen
bonds between complementary base
pairs
2 strands of DNA pair in anti-parallel fashion
with nucleotide bases interacting via
hydrogen bonds in center
Winding of DNA strands creates right-
handed double helix structure
The antiparallel sugar-phosphate strands
twist around each other to form a double
helix
• 10 base pairs per helical turn
• Twisting contributes to energetically favorable
(stable) conformation
Movie 5.1: DNA structure

The complementary structure of DNA

provides a mechanism for both
heredity and protein production
Each base (A, C, T, G) is a letter in a 4-letter
alphabet that is used to spell out biological
messages
All organisms use the same basic 4-letter
alphabet, but the sequences/messages are
different
Most genes contain information to
make proteins
Genetic Code: Set of rules by which
the information contained in the
nucleotide sequence of a gene and its
corresponding RNA molecule is
translated into the amino acid
sequence of a protein
• This will be discussed in more detail in
Chapter 7 (DNA→RNA and
RNA Protein)

The structure of eukaryotic

chromosomes
Each human cell contains about 2 meters of
DNA, which needs to be packed into a nucleus
that is about 5-8 micrometers in diameter
Chromosomes : Eukaryotic structures of
DNA and proteins that package DNA into a
manageable entity
• Bacteria carry genes on a single, circular DNA
molecule—this is also called a “chromosome”
but its packaging and organization is different
from eukaryotic chromosomes—here we are
specifically talking about eukaryotic
chromosomes
All human cells carry 2 copies of each of 23
chromosomes (except gametes: sperm and
eggs, which carry 1 copy of each)
Karyotype: The ordered display of the full
set of 46 (23x2) human chromosomes (ie,
what we see in panel B)

Abnormal chromosomes are

associated with some inherited genetic
disorders.
Chromosomes can be stained different colors
to differentiate them
Cytogeneticists can use these stains to
identify genetic abnormalities, such as
deletions and translocations
Chromosomes organize and carry
genetic information
Chromosomes carry genes
Gene: The segment of DNA that directs
the production of a particular protein
or functional RNA molecule
• Most RNA molecules encoded by genes
are subsequently translated into
 proteins, but in some cases the RNA
molecule may be the final product
Genes may be interspersed by
noncoding DNA, which may help
regulate gene expression or may be
non-functional “junk” DNA
Gene sequences are read 5’→3’; The
complementary strand is not part of
that gene, it may code for a different
gene or it may be non-coding DNA
Genomes
Genome: Total genetic information
carried by all the chromosomes of a
cell or organism
Genome size roughly correlates with
organism complexity, but is not
directly related
• Human genome: 46 chromosomes (23
maternal, 23 paternal)→24,000 genes
 • Bacterial genome: 1
“chromosome” 500 genes
• Chinese muntjac deer has 46
chromosomes, but closely related Indian
munjac deer has 7 chromosomes due to
fusion events during evolution (equal
amounts of DNA/genes)

Specialized DNA Sequences Are

Required for DNA Replication and
Chromosome Segregation
In order to genetic material to be inherited, it
must be able to be copied and segregated into
new cells
Cell cycle: The orderly sequence of events by
which a cell duplicates its contents and
divides into two
➢ This process will be discussed in more detail in
Chapter 18
➢Interphase: Chromosomes are duplicated
➢Mitosis: Chromosomes are segregated into
two daughter cells

Three DNA sequence elements are

needed to produce a eukaryotic
chromosome that can be duplicated
and then segregated at mitosis.
Interphase chromosomes are extended as
long, thin, tangled threads of DNA that are
hard to distinguish
Replication requires 3 DNA elements:
• Replication Origin: Nucleotide sequence at
which DNA replication begins
• Telomere: Repetitive nucleotide sequence that
caps the ends of chromosomes
• Centromere: Specialized DNA sequence that
allows duplicated chromosomes to be separated
during mitosis (M phase)
Mitotic chromosomes are highly
compact
Whereas interphase chromosomes are
elongated for duplication, mitotic
chromosomes are highly compact for more
orderly division
Chromatid refers to the individual
duplicated DNA molecules that are bound
together just prior to mitosis
Centromere: DNA sequence that binds
together two chromatids
Interphase Chromosomes Are Not
Randomly Distributed Within the
Nucleus
Although interphase chromosomes are in
their extended form, they aren’t
unorganized—each occupy their own
territory in the nucleus
Some chromosomes are physically attached
to sites of the nuclear envelope to help
chromosomes remain organized
The nucleolus is the most prominent
structure in the interphase nucleus.
Nucleolus: Large structure within the
nucleus where ribosomal RNA (rRNA) is
transcribed
During interphase, chromosomes with genes
that encode rRNA cluster together to form
the nucleolus,
In the nucleolus, ribosomal RNAs are
synthesized and combine with proteins to
form ribosomes (protein synthesis)
➢ This will be discussed further in Chapter 7
The DNA in Chromosomes Is Always
Highly Condensed
Even during interphase, when DNA is more
extended it is still highly condensed so that it
can fit in the nucleus
• 24mi of thin thread in a tennis ball
• The human genetic code typed out would
be more than 1000 of our cell bio books
During mitosis, it becomes extra condensed
Nucleosomes Are the Basic Units of
Eukaryotic Chromosome Structure
Nucleosome: Bead-like structural unit of a eukaryotic
chromosome composed of a short length of DNA
wrapped around an octameric core of histone
proteins; Includes the histone protein, the DNA
wrapped around it, and the segment of DNA that links
the “beads” together
Histones: A group of abundant, highly conserved
proteins around which DNA wraps to form
nucleosomes (positively charged)
Chromatin: Complex of DNA and proteins that make
up the chromosomes in the cells
Nucleosomes contain DNA wrapped
around a protein core of eight histone
molecules.
• Nuclease: An enzyme that cleaves the
phosphodiester bonds between nucleic
acids
• Will first break the more exposed linker region
before it acts on the more protected bonds
wrapped around the histone core, releasing
nucleosome core particles (histone proteins
plus wrapped DNA)
• High salt will change the chemistry of the
protein interactions to cause dissociation
of the protein-protein complexes and
protein-DNA complexes
• Reveals that the histone complex is an octamer
(8 subunits), made up of 2 molecules of each
H2A, H2B, H3, and H4
 • In the cell histones have a “tail” region that can
undergo temporary covalent modifications to
release DNA

Chromosome Packing Occurs on

Multiple Levels
To further condense mitotic chromatin,
nonhistone chromosomal proteins loop the
chromatin around and clamp the base of each
loop.
DNA packing occurs on several levels
in chromosomes.
Loops are further condensed to
produce mitotic chomatin

Movie 5.2: Chromosome packing

DNA vs Chromatin vs Chromosome vs
Chromatid & Homologous
Chromosome
DNA = nucleic acid material
DNA winds around histone protein octets to
form nucleosome
Nucleosomes get packed in together as
chromatin
The whole length of the strand of DNA and its
structural proteins is a chromosome
During replication, when a chromosome is
duplicated and the two copies are bound
together at the centromere, each copy is a
chromatid
Homologous chromosome is the matched
set of chromosomes that come one from
mother one from father
Regulation of Chromosome structure:
Changes in Nucleosome Structure
Allow Access to DNA
Chromatin-remodeling complex: Enzyme
that uses energy from ATP hydrolysis to alter
the arrangement of nucleosomes in
eukaryotic chromosomes, changing the
accessibility of the underlying DNA to other
proteins
 • During mitosis, many of these complexes are
inactivated, which helps chromosomes maintain
their tightly packed structure
The pattern of modification of histone
tails can determine how a stretch of
chromatin is handled by the cell.
Histone-modifying enzymes: Catalyze the covalent
addition of a small molecule, such as methyl, acetyl, or
phosphoryl groups to a specific amino acid side chain
on a histone tail
• These modifications change the chemistry of the side
chain, to alter the affinity of the protein to the DNA
and altering the tightness of the binding of the DNA to
the histone protein, thereby changing the accessibility
of the region of DNA
• For example: Lysine amino acid is normally positively
charged, and is attracted to negatively charged DNA;
Acetylation neutralizes the positive charge on lysine,
so it is no longer electrostatically drawn to the
negatively charged DNA→DNA is released slightly
Histone tails can also serve as docking site for gene
expression regulatory proteins; Post-translational
modifications (methyl, acetyl, phosphoryl) can impact
binding affinity of those proteins
Interphase Chromosomes Contain both
Highly Condensed and More Extended
Forms of Chromatin
Heterochromatin: Highly condensed
region of interphase chromatin
• Usually gene-poor and transcriptionally
inactive
• Concentrated at centromere and
telomere regions
Euchromatin: Relatively more open
region of interphase chromatin
• Usually more gene-rich
• Its less compact structure allows access
for proteins involved in transcription
Heterochromatin-specific histone
modifications allow heterochromatin
to form and to spread.
Certain modifications to the histone protein
tails promote tight binding to DNA and
condensation of the chromatin
Once the modifying enzyme has been
recruited to a specific region of DNA, it tends
to apply the same heterochromatin
modification to surrounding chromatin, thus
spreading the condensed heterochromatin
state
This extended region of heterochromatin will
continue to spread until it reaches a barrier
sequence, such as a competing modification,
which blocks its further propagation
Once genes are packed away as
heterochromatin, they can be difficult to be
transcribed at all
X-chromosome inactivation
Humans and other mammals with two X-
chromosomes pack one away as
heterochromatin to prevent over-expression
of certain genes
After that X-chromosome has been
inactivated, each daughter cell will inherit
that same inactivation (and the activated X-
chromosome will remain activated in
daughter cell)

The coat color of a calico cat is dictated

in large part by patterns of X-
inactivation.
In cats, one of the genes that specifies coat color is
located on the X-chromosome
In female calico cats, one X-chromosome dictates black
fur and the other dictates orange fur
Skin cells in which the orange X-chromosome is
inactivated will produce black fur, and skin cells in
which the black X-chromosome is inactivated will
produce orange fur
The size of each patch of fur will depend on the
number of skin cells that have descended from an
embryonic cell in which one or the other X-
chromosome was inactivated during development

➢X-inactivation is an extreme example of

heterochromatin, but fine tuning gene expression with
histone modifications is widespread through the
genome
Questions?
• For next class: Read Chapter 6: DNA
Replication and Repair and Journal
Article 2 & 3