the nucleic acids. the history of dna…. friedrich miescher bavarie oswald avery edwin chargaff...

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THE NUCLEIC ACIDS

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Page 1: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

THE NUCLEIC ACIDS

Page 2: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

The history of DNA….

Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins and Franklin Let’s go to Tubingen and Naples

Page 3: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Friedrich Miescher in 1869

isolated what he called nuclein from the nuclei of pus cells

Nuclein was shown to have acidic properties, hence it became called nucleic acid

Chapter 1 …let’s go to Tubingen…

Page 4: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

The circumstantial evidence for DNA… Griffifths Oswald Avery Chapter 3….let’s head to the US….

Page 5: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Transformation:Transformation:Robert Griffith (1928) Robert Griffith (1928)

Page 6: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

DNADNA is the is the TransformeTransformer:r:Avery Avery (1944)(1944)

Page 7: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Hershey-Chase and DNA

The Hershey-Chase ExperimentReview of Griffifth and Hershey-Chase

Page 8: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

There are two types of nucleic acid Deoxyribonucleic acid

(DNA) Ribonucleic acid (RNA)

DNA is found in the nucleus

with small amounts in mitochondria and chloroplasts

RNA is found throughout the cell

Page 9: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

DNA as genetic material: The circumstantial evidence1. Present in all cells and virtually restricted to the nucleus

2. The amount of DNA in somatic cells (body cells) of any given species is constant (like the number of chromosomes)

3. The DNA content of gametes (sex cells) is half that of somatic cells. In cases of polyploidy (multiple sets of chromosomes) the DNA content increases by a proportional factor

4. The mutagenic effect of UV light peaks at 253.7nm. The peak for the absorption of UV light by DNA

Page 10: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

7.1.1 Describe the structure of DNA, including the antiparallel strands, 3’–5’ linkages and hydrogen bonding between purines and pyrimidines

Page 11: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

NUCLEIC ACID STRUCTURE

Nucleic acids are polynucleotides Their building blocks are nucleotides

Page 12: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

NUCLEOTIDE STRUCTURE

PHOSPATE SUGAR

Ribose or Deoxyribose

NUCLEOTIDE

BASEPURINES PYRIMIDINES

Adenine (A)Guanine(G)

Cytocine (C)Thymine (T)Uracil (U)

Page 13: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Ribose is a pentose

C1

C5

C4

C3 C2

O

Page 14: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

RIBOSE DEOXYRIBOSE

CH2OH

H

OH

C

C

OH OH

C

O

H HH

C

CH2OH

H

OH

C

C

OH H

C

O

H HH

C

Spot the difference

Page 15: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

THE SUGAR-PHOSPHATE BACKBONE The nucleotides are all orientated

in the same direction The phosphate group joins the 3rd

carbon of one sugar to the 5th carbon of the next in line.

P

P

P

P

P

P

Page 16: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

ADDING IN THE BASES

The bases are attached to the 1st carbon

Their order is important

It determines the genetic information of the molecule

P

P

P

P

P

P

G

C

C

A

T

T

Page 17: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

DNA IS MADE OF TWO STRANDS OF POLYNUCLEOTIDE

P

P

P

P

P

P

C

G

G

T

A

A

P

P

P

P

P

P

G

C

C

A

T

T

Hydrogen bonds

Page 18: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Working out the structure of DNA…

Page 19: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Let’s bring in Edwin Chargaff…

Chargaff's Ratio's

Page 20: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Erwin Chargaff’s Data (1950-51)

Page 21: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Why the double helix?

Pauling's triple helix

Page 22: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

DNA IS MADE OF TWO STRANDS OF POLYNUCLEOTIDE

The sister strands of the DNA molecule run in opposite directions (antiparallel)

They are joined by the bases Each base is paired with a specific partner:A is always paired with T G is always paired with CPurine with Pyrimidine Thus the sister strands are complementary but not identical The bases are joined by hydrogen bonds, individually weak

but collectively strong

Page 23: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Purines & Pyrimidines

Adenine

CytosineGuanine

Thymine

Page 24: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

James Watson explains base pairing

Page 25: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Watson & Crick Base pairing

Page 26: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

The Double Helix (1953)

© Dr Kalju Kahn USBC Chemistry and BiochemistryPublic Domain image

Page 27: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

Wilkins & Franklin (1952): X-ray crystallography

© Norman Collection on the History of Molecular Biology in Novato, CA

Page 28: THE NUCLEIC ACIDS. The history of DNA…. Friedrich Miescher Bavarie Oswald Avery Edwin Chargaff Meselsohn and Stahl Hershey and Chase Watson, Crick, Wilkins

DNA structure

DNA structure