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Effect of quadruplex DNA formation on repair of endogenous DNA damage
Author(s) -
Beckett Joshua,
Broxson Christopher,
Bloom Linda,
Tornaletti Silvia
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.539.9
Subject(s) - mutagenesis , ap site , dna repair , genome instability , dna , dna damage , ap endonuclease , endonuclease , biology , genomic dna , base excision repair , microbiology and biotechnology , chemistry , mutation , gene , genetics
Quadruplex (G4) DNA is a non canonical four stranded DNA structure that can form in G repeats by stacking of planar arrays of four hydrogen bonded guanines called G quartets. G4‐forming sequences often correspond to genomic regions characterized by genomic instability. We hypothesize that because of its unusual structural properties, G4 DNA may impair the recognition and repair of DNA damage, leading to mutagenesis. To test this hypothesis we have measured the efficiency of repair of abasic (AP) sites, the most common lesion spontaneously generated during cellular metabolism, when they are formed in the G4 forming sequence from the c‐myc gene. We find that removal of a single AP site by human AP endonuclease on the G4 containing substrate was dramatically reduced when the AP site was located in the loop of the G4 structure compared to the unstructured control. This effect was due to decreased enzymatic activity and not to inefficient binding of AP endonuclease to the lesion. Our findings suggest that inefficient repair of lesions formed in G4 DNA may contribute to the mutagenesis associated with these structures.