25

General, Organic, and

Biochemistry, 8e
Bettelheim, Brown
Campbell, and Farrell

© 2006 Thomson Learning, Inc.

All rights reserved
25-1
25Chapter 25

Nucleotides,
Nucleic Acids,
and Heredity

© 2006 Thomson Learning, Inc.

All rights reserved
25-2
25The Molecules of Heredity
• Each cell of our bodies contains thousands of different
proteins.
• How do cells know which proteins to synthesize out of
the extremely large number of possible amino acid
sequences?
• From the end of the 19th century, biologists suspected
that the transmission of hereditary information took
place in the nucleus, more specifically in structures
called chromosomes.
• The hereditary information was thought to reside in
genes within the chromosomes.
• Chemical analysis of nuclei showed chromosomes are
made up largely of proteins called histones and nucleic
acids.
© 2006 Thomson Learning, Inc.
All rights reserved
25-3
25The Molecules of Heredity
• By the 1940s, it became clear that deoxyribonucleic
acids (DNA) carry the hereditary information.
• Other work in the 1940s demonstrated that each gene
controls the manufacture of one protein.
• Thus the expression of a gene in terms of an enzyme
protein led to the study of protein synthesis and its
control.

© 2006 Thomson Learning, Inc.

All rights reserved
25-4
25Nucleic Acids
• There are two kinds of nucleic acids in cells:
• ribonucleic acids (RNA)
• deoxyribonucleic acids (DNA)
• Both RNA and DNA are polymers built from
monomers called nucleotides.
• A nucleotide is composed of:
• a base, a monosaccharide, and a phosphate.

The
sugars
© 2006 Thomson Learning, Inc.
All rights reserved
25-5
Pyrimidine/Purine
25 Bases

© 2006 Thomson Learning, Inc.

All rights reserved
25-6
Nucleosides
25
• Nucleoside: a compound that consists of D-ribose
or 2-deoxy-D-ribose bonded to a purine or
pyrimidine base by a -N-glycosidic bond.

© 2006 Thomson Learning, Inc.

All rights reserved
25-7
25

© 2006 Thomson Learning, Inc.

All rights reserved
25-8
adenosine Deoxyadenosine (dA)
Nucleotides
25
• Nucleotide: a nucleoside in which a molecule of phosphoric
acid is esterified with an -OH of the monosaccharide, most
commonly either the 3’ or the 5’-OH.

© 2006 Thomson Learning, Inc.

All rights reserved
25-9
25Nucleotides
• deoxythymidine 3’-monophosphate (3’-dTMP)

© 2006 Thomson Learning, Inc.

All rights reserved
25-10
25Nucleotides
• adenosine 5’-triphosphate (ATP) serves as a common
currency into which energy gained from food is
converted and stored.

© 2006 Thomson Learning, Inc.

All rights reserved
25-11
25

© 2006 Thomson Learning, Inc.

All rights reserved
25-12
25 DNA and RNA
• The three differences in structure between DNA
and RNA are:
• DNA bases are A, G, C, and T; the RNA bases are A, G,
C, and U.
• The sugar in DNA is 2-deoxy-D-ribose; in RNA it is D-
ribose.
• DNA is always double stranded; there are several kinds
of RNA, all of which are single-stranded.

© 2006 Thomson Learning, Inc.

All rights reserved
25-13
25Structure of DNA and RNA
• Figure 25.2
• Schematic diagram
of a nucleic acid
molecule. The four
bases of each
nucleic acid are
arranged in various
specific
sequences.
• base sequence is
read from the 5’ end
to the 3’ end
© 2006 Thomson Learning, Inc.
All rights reserved
25-14
25DNA - 2° Structure
• Secondary structure: the ordered arrangement of
nucleic acid strands.
• the double helix model of DNA 2° structure was
proposed by James Watson and Francis Crick in 1953.
• Double helix: a type of 2° structure of DNA in
which two polynucleotide strands are coiled
around each other in a screw-like fashion.

© 2006 Thomson Learning, Inc.

All rights reserved
25-15
25The DNA Double Helix
• Figure 25.4
Three-
dimensional
structure of a
DNA double
helix.

© 2006 Thomson Learning, Inc.

All rights reserved
25-16
25Base Pairing

© 2006 Thomson Learning, Inc.

All rights reserved
25-17
25Higher Structure of DNA
• DNA is coiled around proteins called histones.
• Histones are rich in the basic amino acids Lys and Arg,
whose side chains have a positive charge.
• The negatively-charged DNA molecules and positively-
charged histones attract each other and form units
called nucleosomes.
• Nucleosome: a core of eight histone molecules around
which the DNA helix is wrapped.
• Nucleosomes are further condensed into chromatin.
• Chromatin fibers are organized into loops, and the
loops into the bands that provide the superstructure of
chromosomes.

© 2006 Thomson Learning, Inc.

All rights reserved
25-18
25Chromosomes

© 2006 Thomson Learning, Inc.

All rights reserved
25-19
25Chromosomes

© 2006 Thomson Learning, Inc.

All rights reserved
25-20
25Chromosomes

© 2006 Thomson Learning, Inc.

All rights reserved
25-21
25Chromosome

© 2006 Thomson Learning, Inc.

All rights reserved
25-22
25Information Transfer
• Figure 25.9 Information transfer in cells.

© 2006 Thomson Learning, Inc.

All rights reserved
25-23
25RNA
• RNA molecules are classified according to their
structure and function.

© 2006 Thomson Learning, Inc.

All rights reserved
25-24
25Structure of tRNA
• Figure 25.10 Structure of tRNA,

© 2006 Thomson Learning, Inc.

All rights reserved
25-25
25Ribosome
• Figure 25.11
Structure of a
prokaryotic
ribosome.

© 2006 Thomson Learning, Inc.

All rights reserved
25-26
25Genes, Exons, and Introns
• Gene: a segment of DNA that carries a base
sequence that directs the synthesis of a
particular protein, tRNA, or mRNA.
• There are many genes in one DNA molecule.
• In bacteria the gene is continuous.
• In higher organisms the gene is discontinuous.
• Exon: a section of DNA that, when transcribed,
codes for a protein or RNA.
• Intron: a section of DNA or mRNA that does not
code for a protein.

© 2006 Thomson Learning, Inc.

All rights reserved
25-27
25Genes, Exons, and Introns
• Figure 25.12 Prokaryotes; properties of mRNA
molecules during transcription and translation.

© 2006 Thomson Learning, Inc.

All rights reserved
25-28
25Genes, Exons, and Introns
• Figure 25.12 Eukaryotes; properties of mRNA
molecules during transcription and translation.

© 2006 Thomson Learning, Inc.

All rights reserved
25-29
25DNA Replication
• Replication involves separation of the two
original strands and synthesis of two new
daughter strands using the original strands as
templates.
• DNA double helix unwinds at a specific point called an
origin of replication.
• Polynucleotide chains are synthesized in both
directions from the origin of replication; that is, DNA
replication is bidirectional.
• At each origin of replication, there are two replication
forks, points at which new polynucleotide strands are
formed.
© 2006 Thomson Learning, Inc.
All rights reserved
25-30
25DNA Replication
• DNA is synthesized from its 5’ -> 3’ end (from the 3’ -> 5’
direction of the template).
• The leading strand is synthesized continuously in the
5’ -> 3’ direction toward the replication fork.
• The lagging strand is synthesized semidiscontinuously
as a series of Okazaki fragments, also in the 5’ -> 3’
direction, but away from the replication fork.
• Okazaki fragments of the lagging strand are joined by
the enzyme DNA ligase.
• Replication is semiconservative: each daughter strand
contains one template strand and one newly
synthesized strand.

© 2006 Thomson Learning, Inc.

All rights reserved
25-31
25DNA Replication

© 2006 Thomson Learning, Inc.

All rights reserved
25-32
25Replisomes
• Replisomes are assemblies of “enzyme
factories”.

© 2006 Thomson Learning, Inc.

All rights reserved
25-33
25DNA Replication
• 1. Opening up the superstructure.
• During replication, the very condensed superstructure
of chromosomes is opened by a signal transduction
mechanism.
• One step of this mechanism involves acetylation and
deacetylation of key lysine residues.

• Acetylation removes a positive charge and thus

weakens
© 2006 Thomson Learning, Inc. the DNA-histone interactions.
All rights reserved
25-34
25DNA Replication
• 2. Relaxation of higher structures of DNA.
• Tropoisomerases (also called gyrases) facilitate the
relaxation of supercoiled DNA by introducing either
single strand or double strand breaks in the DNA.
• Once the supercoiling is relaxed by this break, the
broken ends are joined and the tropoisomerase
diffuses from the location of the replication fork.

© 2006 Thomson Learning, Inc.

All rights reserved
25-35
25DNA Replication
• 3. Unwinding the DNA double helix.
• Replication of DNA starts with unwinding of the double
helix.
• Unwinding can occur at either end or in the middle.
• Unwinding proteins called helicases attach themselves
to one DNA strand and cause separation of the double
helix.
• The helicases catalyze the hydrolysis of ATP as the
DNA strand moves through; the energy of hydrolysis
promotes the movement.

© 2006 Thomson Learning, Inc.

All rights reserved
25-36
25DNA Replication
• Primer/primases
• Primers are short oligonucleotides— 4 to 15
nucleotides long.
• They are required to start the synthesis of both
daughter strands.
• Primases are enzymes that catalyze the synthesis of
primers.
• Primases are placed at about every 50 nucleotides in
the lagging strand synthesis.

© 2006 Thomson Learning, Inc.

All rights reserved
25-37
25DNA Replication
• DNA polymerases are key enzymes in replication.
• Once the two strands have separated at the replication
fork, the nucleotides must be lined up in proper order
for DNA synthesis.
• In the absence of DNA polymerase, alignment is slow.
• DNA polymerase provides the speed and specificity of
alignment.
• Along the lagging (3’ -> 5’) strand, the polymerases can
synthesize only short fragments, because these
enzymes only work from 5’ -> 3’.
• These short fragments are called Okazaki fragments.
• Joining the Okazaki fragments and any remaining nicks
is catalyzed by DNA ligase.
© 2006 Thomson Learning, Inc.
All rights reserved
25-38
25DNA Repair
• The viability of cells depends on DNA repair
enzymes that can detect, recognize, and repair
mutations in DNA.
• Base excision repair (BER): one of the most
common repair mechanisms.
• A specific DNA glycosylase recognizes the damaged
base.
• It catalyzes the hydrolysis of the -N-glycosidic bond
between the incorrect base and its deoxyribose.
• It then flips the damaged base, completing the excision
• The sugar-phosphate backbone remains intact.

© 2006 Thomson Learning, Inc.

All rights reserved
25-39
25DNA Repair
• BER (cont’d)
• At the AP (apurinic or apyrimidinic) site thus created,
an endonuclease catalyzes the hydrolysis of the
backbone
• An exonuclease liberates the sugar-phosphate unit of
the damaged site
• DNA polymerase inserts the correct nucleotide
• DNA ligase seals the backbone to complete the repair
• NER (nucleotide excision repair) removes and
repairs up to 24-32 units by a similar mechanism
involving a number of repair enzymes

© 2006 Thomson Learning, Inc.

All rights reserved
25-40
25Cloning
• Clone: a genetically identical population.
• Cloning: a process whereby DNA is amplified by
inserting it into a host and having the host
replicate it along with the host’s own DNA.
• Polymerase chain reaction (PCR): an automated
technique for amplifying DNA using a heat-stable
DNA polymerase from a thermophilic bacterium.

© 2006 Thomson Learning, Inc.

All rights reserved
25-41
25Cloning

© 2006 Thomson Learning, Inc.

All rights reserved
25-42
25Nucleic Acids

End
Chapter 25
© 2006 Thomson Learning, Inc.
All rights reserved
25-43