Cast of Characters

• Francis Crick

  X-ray diffraction on polypeptides and proteins

• James Watson

Created the structural model

~Asshole~

• Maurice Wilkins

Worked with X-ray crystallography

First work on X-ray diffraction of DNA

• Rosalind Franklin

• Used x-ray diffraction to obtain pictures of the DNA molecule

• INDEPENDENTLY determined structure

• PERIOD I LOVE HERRRRR

Where Did They Start?

Biochemistry- Some biological molecules, like proteins can form helical structures. Discovered by Linus Pauling, Robert Corey, and Herman Branson.

Transmission Genetics-

• Must be able to replicate

• Must contain information

• Must be variable (alleles)

• Must be relatively stable

Using the molecular information obtained by chemist and the data of Rosalind Franklin:

Previous Discoveries + Physical “Blueprint” = Model of DNA (Sugar phosphate outside, Nitrogenous bases on the inside in pairs)

The 3D Structure of DNA

Nucleotide: 3 Basic Components

Deoxyribonucleic Acid

1. Deoxyribose- sugar

2. Nitrogen base- pyrimidine or purine (5 types)

3. Phosphoric acide- phosphate

Nucleotide = all three components

Nucleotide: Nitrogenous Base

• 
  DNA Base Names have Y in them and so does the Pyrimidine- Pyrimidines have the simple structure of single ring

• Purines have the more complicated structure of the double ring

Nucleotide: Phosphate Groups

• Can have 1, 2, 3 phosphate groups

• the nucleotides loose in the cell have 3 phosphate bases and is used for chemical reaction in the cell: ATP (Adenine Triphosphate)

Single DNA Strands

• DNA is a polymer: A chain of nucleotide monomers

• 5’ End (5 prime end)- the end of the DNA strand thatr has the phosphate group

• 3’ end (3 prime end)- has the three sugars at the end, nucelotides are always added to the 3’ end

• DNA always read 5’ to 3’

• Nucleotide triphosphate is added to a growing DNA strand by an enzyme called DNA polymerase

• the different ends (5’ and 3’) are called Polarity/ Directionality = chemical polarity with respect to the numbers carbons in the sugar

DNA Duplex

• DNA is two antiparallel and Complementary DNA strands

• 2 stands come together due to complimentary base pairing

• Built by Phosphodiester bonds

Complementary Base Pairs

• Always a pyrimidine (one ring) and a purine (two rings)

  • A-T (or A-U) and C-G (C-G is harder to separate bc three Hydrogen Bonds)

• Complementary Base Pairing by Hydrogen Bonds (Weak bonds)

• EX: 5’ end- TGTA

  • The reverse complementary- ACAT

The Double Helix

• Two strands in a helix

• One helical turn is 3.4 nm

• Each turn has ~10 base pairs

• The diameter is 2nm in width

3D Structure

• DNA is NOT perfectly Symmetrical

• The minor and the major grooves are important for interaction between DNA and proteins

  • Major groove has more interaction

DNA exists as packaged form as chromosomes inside a cell

There are 6 billion bases in our genome which equates to 6 feet of Linear DNA that needs to fit into a nucleus ( ~5-8 micron) (equivalent to fitting 24 mi of string into a tennis ball) ⬇

Happens through DNA Organization

DNA In the Cell

Supercoiling-

• DNA can be supercoiled (over or under winding of DNA)

• Supercoiled can either be positive (over) or negative (under -making the DNA helix more like the ladder)

• Most DNA in most organisms is negatively supercoiled

REMEMBER: When writing the complimentary sequence, you read/write it from 5’ to 3’ (bottom to top)

DNA Organization

Organization starts with…

Supercoiling

• DNA can be supercoiled

• Supercoiled can be either negative or positive

• Most DNA in most organisms is negatively supercoiled during important molecular processes

Nucleosomes and Chromatosomes

• Nucleosomes are made up of a group of eight histones that act as the core- term nucleosome refers to both the histone core and the DNA wrapped around it

  • Histones are highly conserved proteins

  • Protein “tails” are stretches of amino acid that are often places where chemical modification can change uniform protein function.

  • DNA backbone is negatively charged while the histones are positively charged- allows the DNA to cling to the histone core and wrap around it

• Chromatosomes- has the properties of the nucleosomes but now it has Histone 1

  • A bound H1 protein locks DNA into place, there are now two full turns of DNA around the octamer (166 base pairs) forming a chromatosomes

  • H1 acts like scotch tape and keeps DNA in place on the chromatosome

DNA: approx 3 BP per nm length→ “beads on a string”: approx 20 BP per nm

Solenoid Model (30nm Fiber)

• Where the “beads on a string” continue to wind and coil to form…

• Now at 100 BP per nm

Loop and Scaffold Model

• Loops form on a protein scaffold of non- histone proteins

• More condensation of DNA

• The loops/fibers are then coiled around each other

• The chromosome scaffold is a filamentous framework made up of a large
  number of distinct nonhistone scaffold proteins

Steps Laid out:

1. Supercoiling

2. Nucleosomes and chromatosomes

3. Beads on a string

4. Solenoid

5. Loops

6. Coils

7. Loop and Scaffold model