Information Transfer in Cells

• Information encoded in a DNA molecule is transcribed via synthesis of an RNA molecule

• The sequence of the RNA molecule is "read" and is translated into the sequence of amino acids in a protein.

Review of DNA Structure

• What is a nucleoside? • What is a nucleotide? • What forces hold DNA together as a helix?• Why are there two kinds of grooves in a B

DNA helix? • What are the differences between A, B and

Z forms of DNA

DNA (deoxyribonucleic acid)

Building blocks = deoxyribonucleotides

Sugar

Nitrogenous base

phosphate

Ribose

oH

oH

oH

HoCH2

o1

23

4

5

Ribose - a pentose sugar- a furanose ring

- in RNA- in nucleotides for energy

metabolism (ATP)

H

oH

oH

HoCH2

o1

23

4

5

2 deoxyribose - a pentose sugar- a furanose ring

- in DNA

Nitrogenousbase

Phosphate

LinksNucleotide

units

(11.2 Pentoses of Nucleotides)

• D-ribose (in RNA)

• 2-deoxy-D-ribose (in DNA)

• The difference - 2'-OH vs 2'-H

• This difference affects secondary structure and stability

11.1 Nitrogenous Bases

• Pyrimidines – Cytosine (DNA, RNA)

– Uracil (RNA)

– Thymine (DNA)

• Purines – Adenine (DNA, RNA)

– Guanine (DNA, RNA)

Naturally occurring purine derivatives

Properties of Pyrimidines and Purines

• Keto-enol tautomerism

• Strong absorbance of UV light

Guanine

Guanine

Nucleoside

H

oH

oH

HoCH2

o1

23

4

5

Nitrogenousbase

A purine/pyrimidine + deoxyribose or ribose

HoH

HoCH2

o1

23

4

5

N o

N

NH2Cytosine

1

3

2

45

6

‘

‘‘

‘

‘

N-glycosidiclinkage

Cytidine

11.3 Nucleosides

Linkage of a base to a sugar

• Base is linked via a glycosidic bond

• Named by adding -idine to the root name of a pyrimidine or -osine to the root name of a purine

• Sugars make nucleosides more water-soluble than free bases

11.4 Nucleotides

Nucleoside phosphates

• Know the nomenclature

• "Nucleotide phosphate" is redundant!

Deoxyribonucleic acid

DNA is a nucleotide polymer linked by a 3’ to 5’

phosphodiester bondO-P-O-P-O-P-OCH2

1’

2’3’

4’

5’N o

N

NH2

O

O O O

O O O

- - -

HOH

HOH

OCH2

1’

2’3’

4’

Nitrogenous baseO

O

-

O-P-

5’

5’ phosphate

3’ hydroxyl

Single-stranded DNA:

Has polarityHas a hydrophilic sideHas a hydrophobic side

RNA versus DNA - Stability issues

Double-stranded DNA

1) Pair of DNA chains in an antiparallel arrangement

5’ 3’5’3’

2) Sugar-P backbone outside, aromatic rings (bases)inside

3) Bases pair specifically by H-bonding

A pairs with T; G pairs with C[A] = [T] and [G] = [C][purines] = [pyrimidines]

The “canonical” base pairs

• The canonical A:T and G:C base pairs have nearly identical overall dimensions

• A and T share two H-bonds

• G and C share three H-bonds

• G:C-rich regions of DNA are more stable

• Polar atoms in the sugar-phosphate backbone also form H-bonds

Why a helix? Why not a ladder?

• A side view of base pairs shows they are perpendicular to the helix axis

• The heterocyclic bases have flat surfaces which are hydrophobic

• To exclude water from between the rings, we should bring the bases closer together

• One way to model them closer together is to “twist” the ladder into a helix

Right-handed twist~10 base pairs per turnB form DNA helix

Summary: What holds DNA together?

• Sugar-phosphate backbone outside • (1) minimizes electrostatic repulsion, • (2) interacts with water

• Bases inside • (3) hydrogen-bonded • (4) plus base stacking by hydrophobic

interactions

Major and minor grooves

• The "tops" of the bases (as we draw them) line the "floor" of the major groove

• The major groove is large enough to accommodate an alpha helix from a protein

• Regulatory proteins (transcription factors) can recognize the pattern of bases and H-bonding possibilities in the major groove

Comparison of A, B, Z DNA

• A: right-handed, short and broad, pitch is

2.3 A, 11 bp per turn • B: right-handed, longer, thinner, pitch is

~3.4 A, ~10 bp per turn • Z: left-handed, longest, thinnest, pitch is

3.8 A, 12 bp per turn

Picture of E. coli DNA outside of the cell

DNA Packaging

• Human DNA total length is ~2 meters • Is packaged into a nucleus that is ~ 5

microns in diameter • This represents a compression of more

than 100,000 fold• It is made possible by wrapping the DNA

around protein spools called nucleosomes and then packing these into helical filaments

We reviewed:

Chapter 11, Sections: 11.1, 11.2, 11.3, 11.4, 11.5 and the “DNA parts” of 11.6

Chapter 12, Sections: 12.2, 12.5