Trinucleotide repeat deletion via a unique hairpin bypass by DNA polymerase β and alternate flap cleavage by flap endonuclease 1.

ABSTRACT: Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegenerative diseases and prostate cancer. Recent studies have pointed to a linkage between oxidative DNA damage, base excision repair (BER) and TNR expansion, which is demonstrated by the observation that DNA polymerase β (pol β) gap-filling synthesis acts in concert with alternate flap cleavage by flap endonuclease 1 (FEN1) to mediate CAG repeat expansions. In this study, we provide the first evidence that the repair of a DNA base lesion can also contribute to CAG repeat deletions that were initiated by the formation of hairpins on both the template and the damaged strand of a continuous run of (CAG)(20) or (CAG)(25) repeats. Most important, we found that pol β not only bypassed one part of the large templ

SUBMITTER: Xu M 

PROVIDER: S-EPMC3561997 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature