Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Base Excision Repair of Trinucleotide Repeat DNA

The expansion of trinucleotide repeat DNA leads to a multitude of neurodegenerative disorders, where CAG/CTG expansion leads to the onset of Huntington’s Disease (1). Interestingly, in mouse model studies, 8-oxo-7,8-dihydroguanine glycosylase (OGG1) has been implicated in the expansion mechanism of CAG/CTG repeats in the huntingtin gene (2). OGG1, a glycosylase enzyme, is responsible for initiating the base excision repair (BER) pathway by removal of an 8-oxo-7,8-dihydroguanine (8-oxoG) lesion. AP endonuclease (APE1) processes the abasic site created by OGG1 to cleave the DNA backbone and further the BER pathway; polymerase β and DNA ligase then complete the repair event. In vitro, it has been shown that DNA containing CAG or CTG trinucleotide repeats has the ability to form non-B type conformations; more specifically they have been shown to adopt hairpin conformations (3). Recent work done in our laboratory has shown that the guanine located in the loop region of these DNA hairpins is highly susceptible to oxidation (4). Given these observations, the aim of this work is to characterize the BER pathway on trinucleotide repeat hairpin and duplex DNA constructs. Here we have examined the activity of OGG1 and APE1 on trinucleotide repeat substrates containing an 8-oxoG lesion.


  1. Huntington Disease Collaborative Research Group, Cell 72, 971-983, (1993).
  2. I.V. Kovtun, Y. Liu, M. Bjoras, A. Klungland, S.H. Wilson, and C.T. McMurray, Nature 447, 447-452, (2007)
  3. A.M. Gacy, G. Goellner, N. Juranic, S. Macura, C.T. McMurray, Cell 81, 533-540 (1995)
  4. D. Jarem, N. Wilson, and S. Delaney, Biochemistry 48, 6655-6663, (2009).

Kelly Schermerhorn
Sarah Delaney

Department of Chemistry
Brown University
Providence, RI 02912

Ph: 401-863-2044