OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells Article

Kovtun, IV, Liu, Y, Bjoras, M et al. (2007). OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells . NATURE, 447(7143), 447-452. 10.1038/nature05778

cited authors

  • Kovtun, IV; Liu, Y; Bjoras, M; Klungland, A; Wilson, SH; McMurray, CT

authors

abstract

  • 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. ©2007 Nature Publishing Group.

publication date

  • May 24, 2007

published in

Digital Object Identifier (DOI)

start page

  • 447

end page

  • 452

volume

  • 447

issue

  • 7143