Structure, replication and repair of DNA

Chapter 10

• On Feb. 28, 1953 Watson and Crick discovered the structure of DNA

• Nearly beaten to the discovery by Rosalind Franklin (she would have won if she had not been socially isolated)

• Chemical make up had been known for 30 years, but not the three-dimensional structure, which would give a clue as to how it worked.

• Nucleotides - sugar-phosphate backbone and nitrogenous bases.

Chargaff’s Rules

• The amount of A = amount of T• The amount of C = amount of G

New bases always add on to the 3’ end of the molecule,

What is a gene?A section of the DNA that carries informationOne gene – one enzyme or one protein

-- set of related polypeptides or enzymes

• DNA replication is semiconservative – each strand acts as a template for building the complimentary strand.

• Each new molecule contains half of the original DNA.

Semiconservative replication

• There are one or more spots on a DNA molecule where replication always begins.

• These are called origins of replication.

• The most studied DNA belongs to a bacterium called Escherichia coli.

Bacterial DNA

Replication forks are the areas where the DNA “unzips” and is copied.

Joining small molecules (like nucleotides) together to make large molecules is called polymerization, and the large molecules are polymers.

DNA polymerase – enzyme that joins nucleotides

DNA always replicates by adding to the 3’ end.

DNA polymerase needs something to add the nucleotides to.

A primase copies short pieces of DNA as RNA – primer.

DNA polymerase then joins DNA nucleotides to the primer.

When it meets the primer, it replaces it with DNA.

The ends are joined by an enzyme called DNA ligase.

• Eukaryotic DNA is much longer than prokaryotic DNA.

• Each chromosome has many origins of replication where DNA is copied.

• It is easy to copy the 5’ to 3’ or leading strand of DNA, but what about the 3’ to 5’ or lagging strand?

Okazaki fragments

A T G C T C G A C T A G C A A C G T A GT A C G A G C T G A T C G T T G C A T C

Mutations• A mutation is a permanent, inheritable

change in the DNA.• To be passed on to the next generation,

this mutation must be present in the gametes (eggs or sperm).

• Mutagens are factors that speed up the rate of mutation formation

• Mutation rate• Mutation hot spots

Types of mutations

• Point mutations – one to a few base changes

• Chromosomal mutations – large sections of chromosomes are alteredPoint mutations can be:– Base substitutions– Insertions– Deletions

• Chromosomal mutations can be– deficiencies – deletions of many nucleotides– Translocations – sections of DNA moved to

another chromosome– Inversions – a section of DNA turned upside

down– Duplications – large sections appear twice– Aneuploidy

THEDOGSAWTHECATTHEDOGSAWTHYCATTHEDOGSAWTHECOTTHEDOGSAWTHECAT

A THEDOGASAWTHECAT

THE DOG ASA WTH ECA T THEDOGSAWTHECAT THO GSA WTH ECA T

THEDOHOWAREYOUGSAWTHECAT

Why don’t we see more mutations?

• Silent mutations can occur in non-coding (“junk” ) DNA.

• If we change the last codon, in many cases we get the same amino acid.

• We have pairs of chromosomes, so a good gene may “cover” for a bad one.

• We have about 50 enzymes that “police” our DNA looking for changes and fixing them.

Factors that cause mutations:

• Naturally occurring • Radiation• Chemicals• Viruses