Welcome Each of
You to My
Molecular Biology
Class
Molecular Biology of the Gene,
5/E --- Watson et al,(2004)
Part I,Chemistry and Genetics
Part II,Maintenance of the Genome
Part III,Expression of the Genome
Part IV,Regulation
Part V,Methods
3/08/05
Part II,Maintenance of the Genome
Dedicated to the structure of
DNA and the processes that
propagate,maintain and alter it
from one cell generation to the
next
Maintenance of the Genome
Ch 6,The structures of DNA and RNA
Ch 7,Chromosomes,chromatins and
the nucleosome
Ch 8,The replication of DNA
Ch 9,The mutability and repair of DNA
Ch 10,Homologous recombination at
the molecular level
Ch 11,Site-specific recombination and
transposition of DNA
3/08/05
CHAPTER 6
The Structures of
DNA and RNA
How do the structures of DNA
and RNA account for their
functions?
OUTLINE
1.DNA Structure
2.DNA Topology
3.RNA Structure
DNA STRUCTURE
DN
A
S
TR
UC
TU
RE
(
1)
DNA is composed of
polynucleotide chains
Structure,twisting around each
other in the form of a double helix.
Schematic model Space-filling model
Nucleoside & Nucleotide,the
fundamental building block of DNA
glycosidic bond
phosphoester bond
DNA polarity,is defined by the asymmetry of the
nucleotides and the way they are joined.
Phosphodiester linkages,repeating,sugar-phosphate
backbone of the polynucleotide chain
Bases in DNA
purines
pyrimidines
adenine
guanine
cytosine
thymine
N9
N1
DN
A
S
TR
UC
TU
RE
(
2)
Each bases has its preferred
tautomeric form (Related to Ch 9)
The two strands of the double helix are
held together by base pairing in an
antiparallel orientation,Which is a
stereochemical consequence of the way that
adenine and thymine,and guanine and cytosine,
pair with each other,(Related to replication
and transcription)
DN
A
S
TR
UC
TU
RE
(
3)
The Two Chains of the Double Helix
Have Complementary Sequences
Example,If sequence 5’-ATGTC-3’ on
one chain,the opposite chain must
have the complementary sequence 3’-
TACAG-5’
DN
A
S
TR
UC
TU
RE
(
4)
Watson-Crick Base Pairing
(Related to replication and transcription)
The strictness of the rules for,Waston-Crick” pairing
derives from the complementarity both of shape and
of hydrogen bonding properties between adenine
and thymine and between guanine and cytosine.
A:C incompatibility
Hydrogen Bonding Is Important
for the Specificity of Base Pairing
DN
A
S
TR
UC
TU
RE
(
5)
? The hydrogen bonds between
complementary bases contribute to
the thermodynamic stability of the
helix (why?) and the specificity of
base pairing
? Stacking interactions between bases
significantly contribute to the stability
of DNA double helix
The double helix has Minor and
Major grooves (What & Why)
DN
A
S
TR
UC
TU
RE
(
5) (See the Structural
Tutorial of this
chapter for details)
It is a simple
consequence of the
geometry of the
base pair.
The Major groove is rich in chemical
information
(What are the biological relevance?)
DN
A
S
TR
UC
TU
RE
(
6)
The edges of each base pair are exposed
in the major and minor grooves,creating a
pattern of hydrogen bond donors and
acceptors and of van der Waals surfaces
that identifies the base pair.
A,H-bond acceptors D,H-bond donors
H,non-polar hydrogens M,methyl groups
The double helix exists in multiple
conformations.
DN
A
S
TR
UC
TU
RE
(
7)
? The B form (10 bp/turn),which is
observed at high humidity,most closely
corresponds to the average structure of
DNA under physiological conditions
?A form (11 bp/turn),which observed
under the condition of low humidity,
presents in certain DNA/protein
complexes,RNA double helix adopts a
similar conformation,
DNA strands can separate
(denature) and reassociate (anneal)
DN
A
S
TR
UC
TU
RE
(
8)
Key terms to understand
1.Denaturation
2.Hybridization
3.Annealing/renature
4.Absorbance
5.Hyperchromicity
6.Tm (melting point)
DNA TOPOLOGY
DN
A
T
OP
OL
OGY
(
1)
Structure (1),Linking number is an
invariant topological property of
covalently closed,circular DNA
(cccDNA)
Linking number is the number of
times one strand have to be passed
through the other strand in order for
the two strands to be entirely
separated from each other.
Species of cccDNA
1,Plasmid and circular bacterial
chromosomes
2,Linear DNA molecules of eukaryotic
chromosomes due to their extreme
length,entrainment in chromatin and
interaction with other cellular
components (Ch 7)
Structure (2),Linking number is
composed of Twist and Writhe
The linking number is the sum of the
twist and the writhe.
Twist is the number of times one strand
completely wraps around the other
strand.
Writhe is the number of times that the
long axis of the double helical DNA
crosses over itself in 3-D space.
DN
A
T
OP
OL
OGY
(
2)
Local
disruption
of base
pairs
Function (1),DNA in cells is negatively
supercoiled; nucleosomes introduces
negative supercoiling in eukaryotes
Negative supercoils serve as a store of
free energy that aids in processes that
require strand separation,such as DNA
replication and transcription,Strand
separation can be accomplished more
easily in negatively supercoiled DNA than
in relaxed DNA
DN
A
T
OP
OL
OGY
(
3)
Function (2),Topoisomerases
(P115-119)
1,The biological importance of
topoisomerase?
2,The functional difference of the two
types of topoisomerases?
3,The working mechanism of
topoisomerase (See the animation for
detail)
DN
A
T
OP
OL
OGY
(
4)
RNA STRUCTURE
RN
A
S
TR
UC
TU
RE
(
1)
RNA contains ribose and uracil and is
usually single-stranded
Biological roles of RNA
1,RNA is the genetic material of some viruses
2,RNA functions as the intermediate (mRNA)
between the gene and the protein-synthesizing
machinery.
3,RNA functions as an adaptor (tRNA) between
the codons in the mRNA and amino acids.
4,RNA serves as a regulatory molecule,which
through sequence complementarity binds to,
and interferes with the translation of certain
mRNAs.
5,Some RNAs are enzymes that catalyze essential
reactions in the cell (RNase P ribozyme,large
rRNA,self-splicing introns,etc).
Structure (1),RNA chains fold back on
themselves to form local regions of double
helix similar to A-form DNA
RNA
S
TR
UC
TU
RE
(
2)
hairpin
bulge
loop
RNA helix are the base-
paired segments between
short stretches of
complementary sequences,
which adopt one of the
various stem-loop
structures
Some tetraloop sequence can enhance the
stability of the RNA helical structures
For example,UUCG loop is unexpectedly stable
due to the special base-stacking in the loop
Pseudoknots are complex structure
resulted from base pairing of
discontiguous RNA segments
Figure 6-32 Pseudoknot.
Non-Watson-Crick G:U base pairs represent
additional regular base pairing in RNA,which
enriched the capacity for self-complementarity
Figure 6-33 G:U base pair
The double helical structure of RNA resembles
the A-form structure of DNA.
The minor groove is wide and shallow,but
offers little sequence-specific information,
The major groove is so narrow and
deep that it is not very accessible to
amino acid side chains from interacting
proteins,Thus RNA structure is less well
suited for sequence-specific interactions
with proteins
Structure (2),RNA can fold up into complex
tertiary structures
RNA
S
TR
UC
TU
RE
(
3)
RNA has enormous rotational freedom in
the backbone of its non-base-paired
regions
Why?
Interactions in the tertiary structure
? Unconventional base pairing,such as base
triples,base-backbone interactions
? Proteins can assist the formation of
tertiary structures by large RNA molecule
The crystal structure of a 23S ribosme
Function,Some RNAs are enzymes
RNA
S
TR
UC
TU
RE
(
4)
Ribozymes are RNA molecules that
adopt complex tertiary structure and
serve as biological catalysts.
RNase P and self-splicing introns are
ribozymes
Structure & Function,The hammerhead
ribozyme cleaves RNA by formation of a
2’,3’ cyclic phophate
RNA
S
TR
UC
TU
RE
(
5)
See animation for detail
Homework (on the CD)
1,See the animations for DNA topology,
Topoisomerase,as well as Ribozyme
Structure and Activity,Answering the
questions in,applying your knowledge”
is required.
2,Play the structural tutorial
“Introduction to the DNA structure” to
better understand DNA structure
3,Finish all the critical thinking exercise
Key points for Chapter 6
1.Definitions,topoisomerase,
ribozyme,double helix,DNA
denaturation,Tm,linking number,
pseudoknot,
2.What are the structural differences
between DNA and RNA? How the
structural properties of DNA and
RNA determine their distinct
biological functions,
You to My
Molecular Biology
Class
Molecular Biology of the Gene,
5/E --- Watson et al,(2004)
Part I,Chemistry and Genetics
Part II,Maintenance of the Genome
Part III,Expression of the Genome
Part IV,Regulation
Part V,Methods
3/08/05
Part II,Maintenance of the Genome
Dedicated to the structure of
DNA and the processes that
propagate,maintain and alter it
from one cell generation to the
next
Maintenance of the Genome
Ch 6,The structures of DNA and RNA
Ch 7,Chromosomes,chromatins and
the nucleosome
Ch 8,The replication of DNA
Ch 9,The mutability and repair of DNA
Ch 10,Homologous recombination at
the molecular level
Ch 11,Site-specific recombination and
transposition of DNA
3/08/05
CHAPTER 6
The Structures of
DNA and RNA
How do the structures of DNA
and RNA account for their
functions?
OUTLINE
1.DNA Structure
2.DNA Topology
3.RNA Structure
DNA STRUCTURE
DN
A
S
TR
UC
TU
RE
(
1)
DNA is composed of
polynucleotide chains
Structure,twisting around each
other in the form of a double helix.
Schematic model Space-filling model
Nucleoside & Nucleotide,the
fundamental building block of DNA
glycosidic bond
phosphoester bond
DNA polarity,is defined by the asymmetry of the
nucleotides and the way they are joined.
Phosphodiester linkages,repeating,sugar-phosphate
backbone of the polynucleotide chain
Bases in DNA
purines
pyrimidines
adenine
guanine
cytosine
thymine
N9
N1
DN
A
S
TR
UC
TU
RE
(
2)
Each bases has its preferred
tautomeric form (Related to Ch 9)
The two strands of the double helix are
held together by base pairing in an
antiparallel orientation,Which is a
stereochemical consequence of the way that
adenine and thymine,and guanine and cytosine,
pair with each other,(Related to replication
and transcription)
DN
A
S
TR
UC
TU
RE
(
3)
The Two Chains of the Double Helix
Have Complementary Sequences
Example,If sequence 5’-ATGTC-3’ on
one chain,the opposite chain must
have the complementary sequence 3’-
TACAG-5’
DN
A
S
TR
UC
TU
RE
(
4)
Watson-Crick Base Pairing
(Related to replication and transcription)
The strictness of the rules for,Waston-Crick” pairing
derives from the complementarity both of shape and
of hydrogen bonding properties between adenine
and thymine and between guanine and cytosine.
A:C incompatibility
Hydrogen Bonding Is Important
for the Specificity of Base Pairing
DN
A
S
TR
UC
TU
RE
(
5)
? The hydrogen bonds between
complementary bases contribute to
the thermodynamic stability of the
helix (why?) and the specificity of
base pairing
? Stacking interactions between bases
significantly contribute to the stability
of DNA double helix
The double helix has Minor and
Major grooves (What & Why)
DN
A
S
TR
UC
TU
RE
(
5) (See the Structural
Tutorial of this
chapter for details)
It is a simple
consequence of the
geometry of the
base pair.
The Major groove is rich in chemical
information
(What are the biological relevance?)
DN
A
S
TR
UC
TU
RE
(
6)
The edges of each base pair are exposed
in the major and minor grooves,creating a
pattern of hydrogen bond donors and
acceptors and of van der Waals surfaces
that identifies the base pair.
A,H-bond acceptors D,H-bond donors
H,non-polar hydrogens M,methyl groups
The double helix exists in multiple
conformations.
DN
A
S
TR
UC
TU
RE
(
7)
? The B form (10 bp/turn),which is
observed at high humidity,most closely
corresponds to the average structure of
DNA under physiological conditions
?A form (11 bp/turn),which observed
under the condition of low humidity,
presents in certain DNA/protein
complexes,RNA double helix adopts a
similar conformation,
DNA strands can separate
(denature) and reassociate (anneal)
DN
A
S
TR
UC
TU
RE
(
8)
Key terms to understand
1.Denaturation
2.Hybridization
3.Annealing/renature
4.Absorbance
5.Hyperchromicity
6.Tm (melting point)
DNA TOPOLOGY
DN
A
T
OP
OL
OGY
(
1)
Structure (1),Linking number is an
invariant topological property of
covalently closed,circular DNA
(cccDNA)
Linking number is the number of
times one strand have to be passed
through the other strand in order for
the two strands to be entirely
separated from each other.
Species of cccDNA
1,Plasmid and circular bacterial
chromosomes
2,Linear DNA molecules of eukaryotic
chromosomes due to their extreme
length,entrainment in chromatin and
interaction with other cellular
components (Ch 7)
Structure (2),Linking number is
composed of Twist and Writhe
The linking number is the sum of the
twist and the writhe.
Twist is the number of times one strand
completely wraps around the other
strand.
Writhe is the number of times that the
long axis of the double helical DNA
crosses over itself in 3-D space.
DN
A
T
OP
OL
OGY
(
2)
Local
disruption
of base
pairs
Function (1),DNA in cells is negatively
supercoiled; nucleosomes introduces
negative supercoiling in eukaryotes
Negative supercoils serve as a store of
free energy that aids in processes that
require strand separation,such as DNA
replication and transcription,Strand
separation can be accomplished more
easily in negatively supercoiled DNA than
in relaxed DNA
DN
A
T
OP
OL
OGY
(
3)
Function (2),Topoisomerases
(P115-119)
1,The biological importance of
topoisomerase?
2,The functional difference of the two
types of topoisomerases?
3,The working mechanism of
topoisomerase (See the animation for
detail)
DN
A
T
OP
OL
OGY
(
4)
RNA STRUCTURE
RN
A
S
TR
UC
TU
RE
(
1)
RNA contains ribose and uracil and is
usually single-stranded
Biological roles of RNA
1,RNA is the genetic material of some viruses
2,RNA functions as the intermediate (mRNA)
between the gene and the protein-synthesizing
machinery.
3,RNA functions as an adaptor (tRNA) between
the codons in the mRNA and amino acids.
4,RNA serves as a regulatory molecule,which
through sequence complementarity binds to,
and interferes with the translation of certain
mRNAs.
5,Some RNAs are enzymes that catalyze essential
reactions in the cell (RNase P ribozyme,large
rRNA,self-splicing introns,etc).
Structure (1),RNA chains fold back on
themselves to form local regions of double
helix similar to A-form DNA
RNA
S
TR
UC
TU
RE
(
2)
hairpin
bulge
loop
RNA helix are the base-
paired segments between
short stretches of
complementary sequences,
which adopt one of the
various stem-loop
structures
Some tetraloop sequence can enhance the
stability of the RNA helical structures
For example,UUCG loop is unexpectedly stable
due to the special base-stacking in the loop
Pseudoknots are complex structure
resulted from base pairing of
discontiguous RNA segments
Figure 6-32 Pseudoknot.
Non-Watson-Crick G:U base pairs represent
additional regular base pairing in RNA,which
enriched the capacity for self-complementarity
Figure 6-33 G:U base pair
The double helical structure of RNA resembles
the A-form structure of DNA.
The minor groove is wide and shallow,but
offers little sequence-specific information,
The major groove is so narrow and
deep that it is not very accessible to
amino acid side chains from interacting
proteins,Thus RNA structure is less well
suited for sequence-specific interactions
with proteins
Structure (2),RNA can fold up into complex
tertiary structures
RNA
S
TR
UC
TU
RE
(
3)
RNA has enormous rotational freedom in
the backbone of its non-base-paired
regions
Why?
Interactions in the tertiary structure
? Unconventional base pairing,such as base
triples,base-backbone interactions
? Proteins can assist the formation of
tertiary structures by large RNA molecule
The crystal structure of a 23S ribosme
Function,Some RNAs are enzymes
RNA
S
TR
UC
TU
RE
(
4)
Ribozymes are RNA molecules that
adopt complex tertiary structure and
serve as biological catalysts.
RNase P and self-splicing introns are
ribozymes
Structure & Function,The hammerhead
ribozyme cleaves RNA by formation of a
2’,3’ cyclic phophate
RNA
S
TR
UC
TU
RE
(
5)
See animation for detail
Homework (on the CD)
1,See the animations for DNA topology,
Topoisomerase,as well as Ribozyme
Structure and Activity,Answering the
questions in,applying your knowledge”
is required.
2,Play the structural tutorial
“Introduction to the DNA structure” to
better understand DNA structure
3,Finish all the critical thinking exercise
Key points for Chapter 6
1.Definitions,topoisomerase,
ribozyme,double helix,DNA
denaturation,Tm,linking number,
pseudoknot,
2.What are the structural differences
between DNA and RNA? How the
structural properties of DNA and
RNA determine their distinct
biological functions,
