Instability of CTG repeats is governed by the position of a DNA base lesion through base excision repair.

ABSTRACT: Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegeneration and cancer. However, their underlying mechanisms remain to be elucidated. Recent studies have demonstrated that CAG repeat expansions can be initiated by oxidative DNA base damage and fulfilled by base excision repair (BER), suggesting active roles for oxidative DNA damage and BER in TNR instability. Here, we provide the first evidence that oxidative DNA damage can induce CTG repeat deletions along with limited expansions in human cells. Biochemical characterization of BER in the context of (CTG)20 repeats further revealed that repeat instability correlated with the position of a base lesion in the repeat tract. A lesion located at the 5'-end of CTG repeats resulted in expansion, whereas a lesio

SUBMITTER: Lai Y 

PROVIDER: S-EPMC3582642 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature