Securing genome stability by orchestrating DNA repair: removal of radiation-induced clustered lesions in DNA.
In addition to double- and single-strand DNA breaks and isolated base modifications, ionizing radiation induces clustered DNA damage, which contains two or more lesions closely spaced within about two helical turns on opposite DNA strands. Post-irradiation repair of single-base lesions is routinely performed by base excision repair and a DNA strand break is involved as an intermediate. Simultaneous processing of lesions on opposite DNA strands may generate double-strand DNA breaks and enhance nonhomologous end joining, which frequently results in the formation of deletions. Recent studies support the possibility that the mechanism of base excision repair contributes to genome stability by diminishing the formation of double-strand DNA breaks during processing of clustered lesions.
Dianov
G L
GL
MRC Radiation & Genome Stability Unit, Harwell, UK. g.dianov@har.mrc.ac.uk
O'Neill
P
P
Goodhead
D T
DT
D000818:Animals; D019757:Carbon-Oxygen Lyases / Q000378:metabolism; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D045647:DNA Glycosylases; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D016678:Genome; D006801:Humans; D008954:Models, Biological; D009699:N-Glycosyl Hydrolases / Q000378:metabolism
D004247:DNA; D043223:Deoxyribonuclease IV (Phage T4-Induced); D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase