| First Author | Xu M | Year | 2013 |
| Journal | Nucleic Acids Res | Volume | 41 |
| Issue | 3 | Pages | 1684-97 |
| PubMed ID | 23258707 | Mgi Jnum | J:200226 |
| Mgi Id | MGI:5507906 | Doi | 10.1093/nar/gks1306 |
| Citation | Xu M, et al. (2013) Trinucleotide repeat deletion via a unique hairpin bypass by DNA polymerase beta and alternate flap cleavage by flap endonuclease 1. Nucleic Acids Res 41(3):1684-97 |
| abstractText | 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 beta (pol beta) 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 beta not only bypassed one part of the large template hairpin but also managed to pass through almost the entire length of small hairpin. The unique hairpin bypass of pol beta resulted in large and small deletions in coordination with FEN1 alternate flap cleavage. Our results provide new insight into the role of BER in modulating genome stability that is associated with human diseases. |
