| First Author | Kovtun IV | Year | 2007 |
| Journal | Nature | Volume | 447 |
| Issue | 7143 | Pages | 447-52 |
| PubMed ID | 17450122 | Mgi Jnum | J:122765 |
| Mgi Id | MGI:3715413 | Doi | 10.1038/nature05778 |
| Citation | Kovtun IV, et al. (2007) OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature 447(7143):447-52 |
| abstractText | Although oxidative damage has long been associated with ageing and neurological disease, mechanistic connections of oxidation to these phenotypes have remained elusive. Here we show that the age-dependent somatic mutation associated with Huntington's disease occurs in the process of removing oxidized base lesions, and is remarkably dependent on a single base excision repair enzyme, 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1). Both in vivo and in vitro results support a 'toxic oxidation' model in which OGG1 initiates an escalating oxidation-excision cycle that leads to progressive age-dependent expansion. Age-dependent CAG expansion provides a direct molecular link between oxidative damage and toxicity in post-mitotic neurons through a DNA damage response, and error-prone repair of single-strand breaks. |
