- Nucleotide excision repair
- Specific endonucleases release the oligonucleotides containing damaged bases; DNA polymerase and ligase fill and reseal the gap, respectively.
- Repairs bulky helix-distorting lesions.
- Occurs in G1 phase of cell cycle.
- Defective in xeroderma pigmentosum (inability to repair DNA pyrimidine-pyrimidine dimers caused by [non-ionizing] UV exposure). Findings: dry skin, extreme light sensitivity, skin cancer.
- Base excision repair
- Base-specific Glycosylase removes altered base and creates AP site (apurinic/apyrimidinic). One or more nucleotides are removed by AP-Endonuclease, which cleaves the 5′ end. Lyase cleaves the 3′ end. DNA Polymerase-β fills the gap and DNA Ligase seals it. Occurs throughout cell cycle.
- Important in repair of spontaneous/toxic deamination, depurination, alkylation, oxidation.
- Excess dietary nitrites can promote deamination of cytosine, adenine, guanine to form uracil, hypoxanthine and xanthine respectively.
- “GEL PLease”
- Mismatch repair
- Guided by hypermethylation of parent strand, which helps identify the non-mutated strand for use as a template. Newly synthesized strand is recognized, mismatched nucleotides are removed, and the gap is filled and resealed. Occurs predominantly in S phase of cell cycle.
- Defective in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]).
- Nonhomologous end joining
- Homologous recombination
- Requires two homologous DNA duplexes. A strand from the damaged dsDNA is repaired using a complementary strand from the intact homologous dsDNA as a template. Restores duplexes accurately without loss of nucleotides.
- Defective in breast/ovarian cancers with BRCA1 mutation.
- Bloom syndrome – generalized chromosomal instability with increased susceptibility to neoplasms due to increased crossing-over between homologous chromosomes. Dysfunctional DNA helicase encoded by BLM gene leading. Growth retardation, facial anomalies (microcephaly), photosensitive rash, immunodeficiency (recurrent infections).