DNA Structure/Composition

TaryonoTaryonoFaculty of AgricultureFaculty of Agriculture

Gadjah Mada UniversityGadjah Mada University

Flow of Genetic Information

DNAReplication

RNATranscription

ProteinTranslation

DNADNA Discovery of the Discovery of the DNA double helixDNA double helix

A.A. 1950’s1950’s

B.B. Rosalind FranklinRosalind Franklin - X-ray photo of DNA.- X-ray photo of DNA.

C.C. Watson and CrickWatson and Crick - described the - described the DNA molecule from Franklin’s X-ray.DNA molecule from Franklin’s X-ray.

DNA is the Genetic Material DNA encodes all the information in the cellDNA encodes all the information in the cell The composition of the DNA is the same in all The composition of the DNA is the same in all

cells within an organismcells within an organism Variation among different cells is achieved Variation among different cells is achieved

by reading the DNA differentlyby reading the DNA differently DNA contains four bases that encode all the DNA contains four bases that encode all the

information to make a bacteria or a humaninformation to make a bacteria or a human In some viruses the genetic material is RNAIn some viruses the genetic material is RNA

How is Information Encoded in DNA?

DNA Consists of four kinds of DNA Consists of four kinds of bases (A,C,G,T) joined to a bases (A,C,G,T) joined to a sugar phosphate backbonesugar phosphate backbone

Bases carry the genetic Bases carry the genetic information while the information while the phosphate backbone is phosphate backbone is structuralstructural

Two complementary strands Two complementary strands of bases (C-G) and (A-T)of bases (C-G) and (A-T)

DNA is a Polymer of Deoxyribonucleotide Units

DEOXYRIBONUCLEOTIDE

DEOXY RIBO NUCLEOTIDE

Deoxyribonucleic Acid (DNA)Deoxyribonucleic Acid (DNA)

NucleotideNucleotide::1.1. Phosphate groupPhosphate group2.2. 5-carbon sugar5-carbon sugar3.3. Nitrogenous baseNitrogenous base

~2 nm wide~2 nm wide

DNA NucleotideDNA Nucleotide

OO=P-O O

PhosphatePhosphate GroupGroup

NNitrogenous baseNitrogenous base (A, G, C, or T)(A, G, C, or T)

CH2

O

C1C4

C3 C2

5

SugarSugar(deoxyribose)(deoxyribose)

DNA Double HelixDNA Double Helix

NitrogenousNitrogenousBase (A,T,G or C)Base (A,T,G or C)

““Rungs of ladder”Rungs of ladder”

““Legs of ladder”Legs of ladder”

Phosphate &Phosphate &Sugar BackboneSugar Backbone

DNA Double HelixDNA Double Helix

P

P

P

O

O

O

1

23

4

5

5

3

3

5

P

P

PO

O

O

1

2 3

4

5

5

3

5

3

G C

T A

Nitrogenous BasesNitrogenous Bases PURINESPURINES

1.1. Adenine (A)Adenine (A)

2.2. Guanine (G)Guanine (G)

PYRIMIDINESPYRIMIDINES3.3. Thymine (T)Thymine (T)

4.4. Cytosine (C)Cytosine (C)T or C

A or G

BASE-PAIRINGSBASE-PAIRINGSBaseBase # of # of

PurinesPurines PyrimidinesPyrimidines PairsPairs H-BondsH-BondsAdenine (A)Adenine (A) Thymine (T)Thymine (T) A = TA = T 2 2

Guanine (G)Guanine (G) Cytosine (C)Cytosine (C) C GC G 3 3

CG

3 H-bonds

BASE-PAIRINGSBASE-PAIRINGS

CG

H-bonds

T A

Chargaff’s RuleChargaff’s Rule AdenineAdenine must pair with must pair with ThymineThymine

GuanineGuanine must pair with must pair with CytosineCytosine

Their amounts in a given DNA molecule will be Their amounts in a given DNA molecule will be about the sameabout the same..

G CT A

Backbone Sugar MoleculesDeoxyribose (DNA) Ribose (RNA)

O

OH

HOH

H

H

H

HOCH2

HO

OH

OH

H

H

H

HOCH2

HO H

1´

2´3´

4´

5´1´

2´3´

4´

5´

Ribose= Five Carbon Sugar Molecule

Deoxy ribo nucleotide

The DNA Backbone is a Deoxyribose Polymer

Deoxyribose sugars are linked by Phosphodiester Bonds

OP OO

O-

H2C

O-

O-

OH

OH

H

H

HH

H2C

H2C

HH

H

H

OHH

O

OP OO

OOP

O HH

H

H

OHH

O

HO

5´

3´

5´

5´

3´

3´

2´

2´

2´

1´

1´

1´

5´-p 3´-OH

5´ 3´

5´

3´

5´

3´ 5´

3´OP OO

O-

H2C

O-

O-

OH

OH

H

H

HH

H2C

H2C

HH

H

H

OHH

O

OP OO

OOP

O HH

H

H

OHH

O

HO

5´

3´

5´

5´

3´

3´

2´

2´

2´

1´

1´

1´

OP OO

O-

H2C

O-

O-

OH

OH

H

H

HH

H2C

H2C

HH

H

H

OHH

O

OP OO

OOP

O HH

H

H

OHH

O

HO

5´

3´

5´

5´

3´

3´

2´

2´

2´

1´

1´

1´

Base

Base

Base

OP OO

O-

H2C

O-

O-

OH

OH

H

H

HH

H2C

H2C

HH

H

H

OHH

O

OP OO

OOP

O HH

H

H

OHH

O

HO

5´

3´

5´

5´

3´

3´

2´

2´

2´

1´

1´

1´

NCH

N

NHCN

NH2

O

H

HH

HO

HH

OCH2POO

POO

PO- O-O-

O-O

(dATP)

Deoxyadenosine 5´-triphosphateO

H

HH

HO

HH

NCH

N

NHCN

NH2

HOCH2

DeoxyRibonucleotide

DeoxyRibonucleoside Deoxyadenosine

DNA is Composed of Four Different Ribonucleotides

HN

CHNC

CNC

NCNH2

HHN

CHNC

CNC

NCO

H2N

H

NCC

CHN

C

OCH3

HO

HN

CC

CNC

HO

H

HNH2

Adenine Guanine

Thymine Cytosine

TwoPurines

TwoPyrimidines

9 9

1 1

5´

3´ 5´

3´

NCC

CNC

HO

HNH2

NCC

CHN

C

OCH3

HO

NCC

CHN

C

OCH3

HO

HO

OH

H

H

HHO

P OO

OOP

O

OH

H

H

HH

H2C

H2C

HH

H

H

HO

O-

O-

H2C

O-

OOP

O

T

C

T

A

G

A

Base Pairing Follows:Chargaff’s Rule:Chargaff’s Rule: DNA has equal numbers of thiamines DNA has equal numbers of thiamines

and adenines (A=T) and equal numbers and adenines (A=T) and equal numbers of guanines and cytosines (G=C)of guanines and cytosines (G=C)

Note that in each pair there is one purine and one pyrimidine

A-T G-C

Base Pairing Occurs Through Hydrogen Bonds

A-TG-C

=

G C

A T

Advantages of Double-Stranded Nature of DNA

Forms a stable structureForms a stable structure Hydrophobic bases stack on top of one Hydrophobic bases stack on top of one

another away from solventanother away from solvent Charged phosphate backbone is on the Charged phosphate backbone is on the

outside accessible to solventoutside accessible to solvent Each strand can serve as the template Each strand can serve as the template

For a new strand of DNA (replication)For a new strand of DNA (replication) For an RNA molecule (transcription)For an RNA molecule (transcription)

Double-stranded DNA Forms a Double Helix

Native DNA Forms a B-DNA Helix

Two strands wind about each Two strands wind about each other in a right-handed mannerother in a right-handed manner

Diameter: ~20ÅDiameter: ~20Å Bases per turn: 10 (~34Å)Bases per turn: 10 (~34Å) A major and a minor grooveA major and a minor groove

20Å

Major

Minor

DNA is Highly Packaged within the Cell If the DNA from a single human cell were stretched If the DNA from a single human cell were stretched

out end to end, it would be ~2 meters in lengthout end to end, it would be ~2 meters in length

Cell Nucleus5 x 10-8 M

DNA2 M

(magnified lots of times)

Mechanisms of Packaging Has to be Organized so that DNA can be Untangled for Replication and Has to be Organized so that DNA can be Untangled for Replication and

TranscriptionTranscription SupercoilingSupercoiling Wrapping around Proteins to Create ChromatinWrapping around Proteins to Create Chromatin

Enzymes that Modulate the Packaging of DNA are called TopoisomerasesEnzymes that Modulate the Packaging of DNA are called Topoisomerases

Supercoiling Most native DNA exists in a Most native DNA exists in a negativelynegatively

supercoiled statesupercoiled state This means that it is slightly unwound and it is a bit This means that it is slightly unwound and it is a bit

easier to pull the two strands aparteasier to pull the two strands apart

More supercoiling

Topoisomerases Modulate Supercoiling Topoisomerases act as Molecular ScissorsTopoisomerases act as Molecular Scissors

They can make a cut in the DNA and pass second They can make a cut in the DNA and pass second strand through that break to untangle the DNAstrand through that break to untangle the DNA

DNA is Coiled Around Histone Proteins DNA is wrapped DNA is wrapped

around abundant around abundant nuclear proteins nuclear proteins called called HistonesHistones

This forms a This forms a complex called a complex called a NucleosomeNucleosome

Histones are H1, Histones are H1, H2A, H2B, H3, H4H2A, H2B, H3, H4

DNA is Further Packaged

Take Home Message

DNA is a double helix composed of a sugar-DNA is a double helix composed of a sugar-phosphate backbone and base pairs (a polymer of phosphate backbone and base pairs (a polymer of deoxyribonucleotides)deoxyribonucleotides)

Composition/StructureComposition/Structure DNA is compacted to fit into the cell through:DNA is compacted to fit into the cell through:

SupercoilingSupercoiling Extensive interactions with proteinsExtensive interactions with proteins

These factors all contribute to how the DNA is ReadThese factors all contribute to how the DNA is Read