DNA Repair

Single strand

  • 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]).

Double strand

  • Nonhomologous end joining
    • Brings together 2 ends of DNA fragments to repair double-stranded breaks. No requirement for homology. Some DNA may be lost.
    • Defective in ataxia telangiectasia and Fanconi anemia.
  • 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).

Filipino MD

An independent organization catered to bringing enriching opportunities to doctors, researchers and medical institutions.

TERMS OF SERVICE
ADVERTISE
administrator@filipinomd.com

You cannot copy the contents of this page.