DNA Mutations and Repair Mechanisms

Overview

This section explains sources of DNA mutations and the main cellular mechanisms that repair errors or damage in DNA to maintain genome stability.

DNA polymerase sometimes incorporates the wrong nucleotide during replication, which can result in mutations if not corrected.
Most replication errors are fixed by DNA polymerase’s proofreading activity, which uses 3' exonuclease action to remove incorrect bases.
Mismatch repair corrects errors missed by proofreading by removing and replacing mismatched nucleotides after replication.
In E. coli, mismatch repair distinguishes the new strand by its lack of methylation.
Eukaryotic mismatch repair involves unsealed nicks or lingering replication proteins, with the detailed mechanism still unclear.
Nucleotide excision repair removes damaged, not just mismatched, bases by excising and resynthesizing DNA sections.

Nucleotide excision repair is critical for removing UV-induced thymine dimers that distort DNA structure.
Defects in nucleotide excision repair enzymes cause conditions like xeroderma pigmentosa, resulting in sensitivity to sunlight and increased cancer risk.
Mutations arise not only from replication errors but also from DNA damage by chemical or physical agents (induced) or by natural internal processes (spontaneous).

Point mutations affect single nucleotide pairs and include transitions (purine to purine or pyrimidine to pyrimidine) and transversions (purine to pyrimidine or vice versa).
Silent mutations alter DNA without changing the amino acid due to codon redundancy, typically in the third nucleotide.
Missense mutations change the amino acid, possibly affecting protein function; nonsense mutations introduce premature stop codons.
Insertions or deletions can cause frameshift mutations, altering the reading frame and often creating nonfunctional proteins.
Trinucleotide repeat expansions lead to multiple copies of the same codon and amino acid.
Translocation occurs when DNA segments move to different chromosomes or locations.
Mutations in DNA repair genes can lead to cancer by causing accumulation of somatic mutations or be inherited if present in germ cells.

Proofreading — DNA polymerase activity that removes misincorporated nucleotides using 3' exonuclease function.
Mismatch Repair — System that fixes base-pairing errors post-replication by excising and replacing the faulty region.
Nucleotide Excision Repair — Mechanism removing damaged (often UV-induced) DNA and filling the gap with new nucleotides.
Frameshift Mutation — Mutation from insertion or deletion shifting the reading frame of codons in mRNA.
Silent Mutation — DNA change that does not alter the amino acid sequence of the resulting protein.
Transition — Point mutation replacing a purine with another purine, or pyrimidine with another pyrimidine.
Transversion — Point mutation replacing a purine with a pyrimidine, or vice versa.
Translocation — Movement of a chromosome segment to a new chromosome or location.

Be able to distinguish and describe various mutation types: point, frameshift, silent, missense, nonsense, insertion, deletion, translocation.
Review how DNA repair mechanisms work and identify which errors or damages they correct.
Understand the impact of mutations in repair genes for future study on cancer and genetic disorders.