Discovery of the Double Helix

GeneticsBio 36404

1928 Griffith Experiment

transformation

1944 Avery, MacLeod & McCarty

Centrifuge Heat Blender

proteaseremoves protein

RNAaseremoves RNA

DNAaseremoves DNA

R R R

S

DNA transformsR to S form

1952 Hershey & Chase

DNA not proteinenters bacteria

phageradioactive DNA (P)

phageradioactive DNA

phageradioactive protein (S)

Friedrich Meisner

• 1869• Isolated nucleic acids from white blood

cells

5

Deoxyribose

O

C

CC

C

C O

O

H

HH

HO

H

H

H

HH

OH

2’

Phosphate

P

O

O-

O-

O - P

Bases

GuanineAdenine

Cytosine Thymine

O

NH2

NH2

O

NH2

O

O

CH3

Sugar

Nucleotide

BasePO

1’5’

Sugar

Nucleotide LinkageBaseP

1’5’

BasePO

1’5’

3’

Sugar

O

James Watson (1928 -)

•USA•PhD Zoology Indiana•Copenhagen•Post-Doc phages•Naples Conference - DNA•Cambridge University•Cavindish Lab•Human Genome Project

Francis Crick (1916 - 2004)

•England•Physics•War - Mines•Cambridge University•Cavindish Lab•working on PhD

William L.Bragg

•Director Cavindish Lab at Cambridge•Bragg’s Law - x-ray diffraction•Hemoglobin

John Randall

•Kings College, London•Director Biophysics Unit•DNA

Maurice Wilkins (1916-2004 )

•England•Physics•Manhattan Project•King’s College, London•DNA structure•Naples Conference

Rosalind Franklin (1920 - 1958)•England•PhD Physical Chemistry•France-coal•X-ray diffraction•Kings College •DNA - A and B form•Birkbeck College•Tobacco Mosaic Virus•Aaron Klug

X-ray diffraction

DNA Crystal

X-rays

film

Photo51

Raymond Gosling (1926 -)

•PhD student•Kings College•Wilkins/Franklin

Linus Pauling (1901-1994)

•Cal Tech•Chemist•Protein model

Peter Pauling (1931-2003)

•Son•Cavindish Lab

Erwin Chargaff (1905-2002)

•England•Chemist•Chargaff’s Rules•%G=%C•%A=%T

DNA Model

• Based on all above, Watson and Crick developed double helix model of DNA

• 2 strands running anti-parallel• G pairing with C• A pairing with T

22

DNA Structure

Sugar

GP O1’

5’

Sugar

AP O1’

5’

Sugar

TP O1’

5’

Sugar

C PO

1’5’

Sugar

T PO

1’5’

Sugar

A PO

1’5’

antiparrallel strands

5’

3’

3’

5’

hydrogenbonding

Base Pairing

Guanine

Adenine

O

N

N

O

N

O

O

CH3

Thymine

N NH

HH

CytosineH

H

N H N

HH

HydrogenBonds

Double Helix

• One complete turn 34 A• 20 A diameter• 3.4 A between pairs• A = 10-8 m

25

Publication NatureApril 1953

Nobel Prize 1962Watson, Crick, Wilkins

The Double Helix 1967by James Watson

Other Books• What Mad Pursuit - Francis Crick• The Third Man of the Double Helix -

Maurice Wilkins• The Dark Lady of DNA - Brenda

Maddox• Avoid Boring People - James Watson• DNA - James Watson

29