DNA Replication, Repair, and Genome Stability
Faithful Duplication and Damage Control
Replication mechanics
Replication is semiconservative, bidirectional, and highly coordinated. Leading and lagging strand synthesis, primase action, helicase function, clamp loading, and Okazaki fragment maturation together generate a robust duplication machine.
Core enzymes
Major DNA repair pathways
Base excision repair
- Fixes small, non-helix-distorting lesions
- Uses glycosylases and end processing
Nucleotide excision repair
- Removes bulky lesions
- Excises an oligonucleotide patch
Genome instability
Defects in replication stress response or repair pathway choice can produce mutational signatures, chromosomal rearrangements, and disease susceptibility.
Which repair pathway is especially important for correcting replication mismatches that escape polymerase proofreading?
Mismatch repair recognizes and corrects base mispairs and small insertion-deletion loops after replication.
Correct answer: Mismatch repair
Why is the lagging strand synthesized discontinuously?
Lagging strand synthesis occurs in Okazaki fragments due to antiparallel DNA geometry.
Correct answer: Because DNA polymerase can synthesize only in the direction while the template orientation forces short fragment synthesis
Damage types and likely consequences
| Lesion type | Example consequence |
|---|---|
| Base deamination | Point mutations |
| UV-induced pyrimidine dimers | Replication blockage |
| Double-strand breaks | Rearrangements or loss of chromosome segments |
| Oxidative damage | Mutagenesis and strand interruptions |
What is the principal benefit of homologous recombination repair?
Homologous recombination uses an intact homologous template, making it highly accurate.
Correct answer: It can restore sequence information accurately using a sister chromatid
State one major source of replication stress.
Fork stalling can arise from damage, secondary structures, or nucleotide depletion.
Correct answer: DNA lesions or difficult-to-replicate regions that stall replication forks