Você está na página 1de 30

UNIT VI:

Storage and Expression of


Genetic Information
CHAPTER 29:
DNA Structure, Replication, and Repair
QINGSONG WANG
ASSOCIATE PROFESSOR
DEPT. of BIOCHEMISTRY & MOLECULAR BIOLOGY, HMU

wqs92115@163.com

UNIT VI: Storage and Expression of


Genetic Information

Chapter 29: DNA Structure, Replication and Repair


Chapter 30: RNA Structure, Synthesis and
Processing
Chapter 31: Protein Synthesis
Chapter 32: Regulation of Gene Expression
Chapter 33: Biotechnology and Human Disease

BACKGROUND

NUCLEOTIDE STRUCTURE

I. NUCLEOTIDE STRUCTURE

Nucleotides are composed of a nitrogenous


base, a pentose monosaccharide, and one,
two, or three phosphate groups.
The nitrogencontaining bases belong to two
families of compounds: the purines and the
pyrimidines.
A. Purine and pyrimidine structures
Both DNA and RNA contain the same purine
bases: adenine (A) and guanine (G). Both
DNA and RNA contain the pyrimidine
cytosine (C), but they differ in their second
pyrimidine base: DNA contains thymine (T),
whereas RNA contains uracil (U). T and U
differ in that only T has a methyl group.

Unusual (modified) bases are


occasionally found in some
species of DNA and RNA, for
example, in some viral DNA, and
in transfer RNA. Base
modifications include
methylation, glycosylation,
acetylation, or reduction.

B. Nucleosides
The addition of a pentose sugar to a
base produces a nucleoside. If the
sugar is ribose, a ribonucleoside is
produced; if the sugar is 2deoxyribose, a deoxyribonucleoside
is produced. The ribonucleosides of
A, G, C, and U are named aden
osine, guanosine, cytidine, and
uridine, respectively. The
deoxyribonucleo sides of A, G, C,
and T have the added prefix,
deoxy-, for example,
deoxyadenosine.

C. Nucleotides

The addition of one or more phosphate


groups to a nucleoside produces a
nucleotide. The first phosphate group
is attached by an ester linkage to the
5'-OH of the pentose. The second and
third phosphates are each connected to
the nucleotide by a high-energy
bond.
[Note: The phosphate groups are
responsible for the negative charges
associated with nucleotides, and cause
DNA and RNA to be referred to as
nucleic acids.]

I. OVERVIEW

The flow of information from DNA


to RNA to protein is termed the
central dogma of
molecular biology, and is descriptive
of all organisms, with the exception
of some
viruses that have RNA as the
repository of their genetic
information.

Nucleic acids are required for the


storage and expression of genetic
information.

DNA and RNA

DNA: the repository of genetic


information

Eukaryotic organisms: nucleus,


mitochondria and the chloroplasts of
plants.

Prokaryotic cells, which


lack nuclei, have a single
chromosome

Prokaryotic cells : nucleus, plasmids

What is a chromosome?

The DNA contained in a fertilized egg encodes the


information that directs the development of an
organism. This development may involve the
production of billions of cells.
Each cell is specialized, expressing only those
functions that are required for it to perform its role
in maintaining the organism.
Therefore, DNA must be able to not only replicate
precisely each time a cell divides, but also to have
the information that it contains be selectively
expressed.
Transcription (RNA synthesis) is the first stage in
the expression of genetic information (see Chapter
30).
Next, the code contained in the nucleotide sequence
of messenger RNA molecules is translated (protein
synthesis, see Chapter 31), thus completing gene
expression.
The regulation of gene expression is discussed in
Chapter 32.

II. STRUCTURE OF DNA

DNA is a polymer of deoxyribonucleoside monophosphates


covalently linked by 3'5'phosphodiester bonds.

Single-stranded (ss) DNA & Doublestranded (ds) DNA

The two strands wind around each other, forming a double


helix.

In eukaryotic cells, DNA is found associated with various


types of proteins (known collectively as nucleoprotein) present
in the nucleus, whereas in prokaryotes, the proteinDNA
complex is present in a nonmembrane-bound region known as
the nucleoid.

A. 3'5'- Phosphodiester bonds

B. Double helix

C. Linear and circular DNA molecules

3'5'-Phosphodiester bonds

Figure 29.2
A. DNA chain with the nucleotide sequence shown written in the 5' 3' direction. A 3' 5'-phosphodiester
bond is shown highlighted in the blue box, and the deoxyribose-phosphate backbone is shaded in yellow.
B. The DNA chain written in a more stylized form, emphasizing the ribosephosphate backbone.
C. A simpler representation of the nucleotide sequence. D. The simplest (and most common) representation,
with the abbreviations for the bases written in the conventional 5'3' direction.

Double helix

Double helix

In the double helix, the two chains are coiled around a


common axis called the axis of symmetry.

The chains are paired in an antiparallel manner, that is,


the 5-end of one strand is paired with the 3-end of the
other strand.

In the DNA helix, the hydrophilic


deoxyribosephosphate backbone of each chain is on the
outside of the molecule, whereas the hydrophobic bases
are stacked inside.

The overall structure resembles a twisted ladder.

The spatial relationship between the two strands in the


helix creates a major (wide) groove and a minor (narrow)
groove.

A major (wide) groove and a minor (narrow) groove

The spatial relationship between the two


strands in the helix creates a major (wide)
groove and a minor (narrow) groove.

These grooves provide access for the binding


of regulatory proteins to their specific
recognition sequences along the DNA chain.

Certain anticancer drugs, such as dactinomycin


(actinomycin D), exert their cytotoxic effect by
intercalating into the narrow groove of the
DNA double helix, thus interfering with DNA
and RNA synthesis.

1. Base pairing:

The bases of one strand of DNA are paired


with the bases of the second strand, so that
an adenine is always paired with a thymine
and a cytosine is always paired with a
guanine.

Therefore, one polynucleotide chain of the


DNA double helix is always the complement
of the other. Given the sequence of bases on
one chain, the sequence of bases on the
complementary chain can be determined.

[Note: The specific base pairing in DNA


leads to the Chargaff Rule: In any sample of
dsDNA, the amount of adenine equals the
amount of thymine, the amount of guanine
equals the amount of cytosine, and the total
amount of purines equals the total amount of
pyrimidines.]

The base pairs are held together by


hydrogen bonds: two between A and T
and three between G and C.

These hydrogen bonds, plus the


hydrophobic interactions between the
stacked bases, stabilize the structure
of the double helix.

How is a DNA double helix formed?

Practice Activity

The ribonucleotide polymer -GTGATCAAGCcould only form a double-stranded structure


with:
A) -CACTAGTTCGB) -CACUAGUUCGC) -GCTTGATCACD) -GCUUGAUUAC-

2. Separation of the two DNA strands in the double


helix:
The two strands of the double helix separate when
hydrogen bonds between the paired bases are
disrupted.
Disruption can occur in the laboratory if the pH of the
DNA solution is altered so that the
nucleotide bases ionize, or if the solution is heated.
When DNA is heated, the temperature at which one
half of the helical structure is lost is defined as the
melting temperature (Tm).
The loss of helical structure in DNA, called
denaturation, can be monitored by measuring its
absorbance at 260 nm. Because there are three
hydrogen bonds between G and C but
only two between A and T, DNA that contains high
concentrations of A and T denatures at a lower
temperature than G- and C-rich DNA.
Under appropriate conditions, complementary
DNA strands can reform the double helix by the
process called renaturation (or reannealing).

3. Structural forms of the double helix:


There are three major structural forms of DNA: the B form, described by Watson and Crick in
1953, the A form, and the Z form.
The B form is a right-handed helix with ten residues per 360 turn of the helix, and with the
planes of the bases perpendicular to the helical axis. Chromosomal DNA is thought to consist
primarily of B-DNA (Figure 29.7 illustrates a space-filling model of B-DNA).
The A form is produced by moderately dehydrating the B form. It is also a right-handed helix,
but there are 11 base pairs per turn, and the planes of the base pairs are tilted 20 away from the
perpendicular to the helical axis. The conformation found in DNARNA hybrids or RNARNA
double-stranded regions is probably very close to the A form.
Z-DNA is a left-handed helix that contains about 12 base pairs per turn. Stretches of Z-DNA
can occur naturally in regions of DNA that have a sequence of alternating purines and
pyrimidines, for example, poly GC. Transitions between the B and Z helical forms of DNA may
play a role in regulating gene expression.

C. Linear and circular DNA molecules

Each chromosome in the nucleus of a eukaryote contains one long,


linear molecule of dsDNA, which is bound to a complex mixture of
proteins (histone and non-histone, see p. 409) to form chromatin.

Eukaryotes have closed, circular DNA molecules in their mitochondria, as


do plant chloroplasts.

A prokaryotic organism typically contains a single, double-stranded,


supercoiled, circular chromosome.Each prokaryotic chromosome is
associated with non-histone proteins that can condense the DNA to form a
nucleoid. In addition, most species of bacteria also contain small, circular,
extrachromosomal DNA molecules called plasmids. Plasmid DNA carries
genetic information, and undergoes replication that may or may not be
synchronized to chromosomal division.

Eukaryotic
organisms:
nucleus,
mitochondria and
the chloroplasts of
plants.

Prokaryotic cells,
which
lack nuclei, have a
single
chromosome

Prokaryotic cells :
nucleus, plasmids