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


Trinucleotide repeat (TNR) expansions and deletions are associated ...
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 template hairpin but also managed to pass through almost the entire length of small hairpin. The unique hairpin bypass of pol β 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.





new topics/pols set partial results complete validated


No results available for this paper.

Entry validated by:

Using Polbase tables:


Tables may be sorted by clicking on any of the column titles. A second click reverses the sort order. <Ctrl> + click on the column titles to sort by more than one column (e.g. family then name).


It is also possible to filter the table by typing into the search box above the table. This will instantly hide lines from the table that do not contain your search text.