Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Role of Oxidative DNA Damage and Repair in Triplet Repeat Expansion
Triplet repeat sequences, such as CAG/CTG, expand in the human genome to cause several neurological disorders. The overall objective of our research is to define the molecular mechanism of CAG/CTG triplet repeat expansion. Previous work from other laboratories, using mouse models of triplet repeat diseases, have implicated DNA repair enzymes in the repeat expansion. We have found that the repetitive sequences adopt kinetically-trapped non-B conformations and, furthermore, that these non-B conformations are hyper-susceptible to oxidative damage relative to DNA duplex. Interestingly, despite the presence of hot spots for damage within the non-B conformations we find that base excision repair enzymes are catalytically inactive on these DNA substrates. The implications of these results on triplet repeat expansion will be discussed.