Molecular Biology I Lecture 2-3: DNA Replication and Repair

DNA Structure

• The DNA molecule has a double helix structure with a sugar-phosphate backbone and nitrogenous bases (adenine, guanine, cytosine, and thymine) that pair with each other (A-T and G-C) through hydrogen bonds.
• The distance between each pair of nucleotides is 0.34 nm, and the distance between each turn of the helix is 3.4 nm.

DNA Replication

• Watson and Crick's semiconservative model of replication predicts that each daughter molecule will have one old strand (derived from the parent molecule) and one newly made strand.
• The leading strand is synthesized continuously in the 5' to 3' direction, while the lagging strand is synthesized in short Okazaki fragments that are later joined by DNA ligase.
• DNA polymerase III synthesizes the leading strand, and DNA polymerase I replaces the RNA primer with DNA nucleotides.

Proofreading and Repairing DNA

• DNA polymerases proofread newly made DNA and replace any incorrect nucleotides.
• Mismatch repair corrects errors in base pairing.
• Nucleotide excision repair cuts out and replaces damaged stretches of DNA.
• DNA can be damaged by exposure to harmful chemicals or physical agents, such as cigarette smoke and X-rays.

Telomeres

• Telomeres are the ends of chromosomes that shorten with each cell cycle.
• Telomerase catalyzes the lengthening of telomeres in germ cells.
• The shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions.

Chromosomes

• A chromosome consists of a DNA molecule packed together with proteins.
• Bacterial chromosomes are double-stranded, circular DNA molecules associated with a small amount of protein.
• Eukaryotic chromosomes have linear DNA molecules associated with a large amount of protein.
• Chromatin is a complex of DNA and protein found in the nucleus of eukaryotic cells.

Mutations

• Mutations are changes in the sequence of base pairs in a DNA molecule.
• Point mutations are changes of one or a few base pairs.
• Mutations can occur through spontaneous changes, errors in the replication process, or the action of radiation or particular chemicals.
• A mutation may result in a change to either a DNA base pair or a chromosome.
• A cell with a mutation is a mutant cell.

Types of Mutations

• Somatic mutations occur in somatic cells and affect only the individual in which the mutation occurs.
• Germ-line mutations occur in the germ line of sexually reproducing organisms and can be transmitted to the next generation.
• Base-pair substitutions can be either transition mutations (from one purine-pyrimidine base pair to the other) or transversion mutations (from a purine-pyrimidine base pair to a pyrimidine-purine base pair).

Mutation Rates and Frequencies

• The mutation rate is the probability of a particular kind of mutation as a function of time.
• The mutation frequency is the number of occurrences of a particular kind of mutation, expressed as a proportion of cells or individuals in a population.