DNA Repair Mechanisms

• DNA repair mechanisms address errors during replication and damage to existing DNA.

Replication Error Correction

• Initial pairing mistakes during replication occur at a rate of one error per 100,000 base pairs.
• DNA polymerase proofreads each new nucleotide against the template as it's added.
• Incorrect pairings are removed by the enzyme, which then resumes synthesis.
• Proofreading mechanisms reduce the final error rate to approximately one per ten billion nucleotides.

Sources of DNA Damage

• DNA molecules are constantly exposed to harmful chemical and physical agents.
• Reactive chemicals.
• Radioactive emissions.
• X-rays.
• Ultraviolet (UV) light.
• Exposure can alter nucleotides, affecting encoded genetic information.

Repair Mechanisms

• Mismatched nucleotides missed by DNA polymerase, and mutations after DNA synthesis, can often be repaired.
• Mismatch repair uses special enzymes to fix incorrectly paired nucleotides.
• Nucleotide excision repair involves a nuclease cutting out a segment of the damaged strand.
• DNA polymerase and ligase then fill the gap in nucleotide excision repair.

Cellular Monitoring and Repair

• Cells continuously monitor and repair genetic material using repair enzymes.
• E. coli has 100 known repair enzymes.
• Humans have more than 130 identified repair enzymes.
• Hereditary defects in repair enzymes can lead to conditions such as colon cancer.

Steps in DNA Repair

• Excision: Damage is cut out by a specialized nuclease.
• Resynthesis: The original DNA sequence is restored by a repair DNA polymerase filling the gap.
• Ligation: DNA ligase seals the nick in the sugar-phosphate backbone of the repaired strand.

Consequences of Uncorrected Errors

• Errors during DNA replication need correction to avoid mutations.
• If uncorrected, a mismatch can lead to a permanent mutation in the resulting DNA molecules after replication.

Common Chemical Reactions Causing DNA Damage

• Depurination and deamination are frequent chemical reactions causing serious DNA damage.
• Depurination removes guanine (or adenine) from DNA.
• Deamination converts cytosine to uracil.
• Deamination can also affect other bases.

Thymine Dimers

• Ultraviolet (UV) light can cause thymine dimers between adjacent thymine nucleotides.
• Thymine dimers cause the DNA double helix to buckle and interfere with DNA replication.
• A nuclease enzyme cuts the damaged DNA strand.
• Repair synthesis occurs by a DNA polymerase filling in the missing nucleotides.
• DNA ligase seals the new DNA strand.

Xeroderma Pigmentosum

• Proper functioning of repair enzymes prevents xeroderma pigmentosum, an inherited disorder.
• Individuals with xeroderma pigmentosum are highly sensitive to sunlight.
• Mutations in skin cells are uncorrected, potentially causing skin cancer at a young age.