Deletion of Ogg1 DNA glycosylase results in telomere base damage and length alteration in yeast.
Telomeres consist of short guanine-rich repeats. Guanine can be oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). 8-oxoguanine DNA glycosylase (Ogg1) repairs these oxidative guanine lesions through the base excision repair (BER) pathway. Here we show that in Saccharomyces cerevisiae ablation of Ogg1p leads to an increase in oxidized guanine level in telomeric DNA. The ogg1 deletion (ogg1Delta) strain shows telomere lengthening that is dependent on telomerase and/or Rad52p-mediated homologous recombination. 8-oxoG in telomeric repeats attenuates the binding of the telomere binding protein, Rap1p, to telomeric DNA in vitro. Moreover, the amount of telomere-bound Rap1p and Rif2p is reduced in ogg1Delta strain. These results suggest that oxidized guanines may perturb telomere length equilibrium by attenuating telomere protein complex to function in telomeres, which in turn impedes their regulation of pathways engaged in telomere length maintenance. We propose that Ogg1p is critical in maintaining telomere length homoeostasis through telomere guanine damage repair, and that interfering with telomere length homoeostasis may be one of the mechanism(s) by which oxidative DNA damage inflicts the genome.
Lu
Jian
J
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Liu
Yie
Y
D004247:DNA / Q000378:metabolism; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D006147:Guanine / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D000089804:Shelterin Complex; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C440829:RAP1 protein, S cerevisiae; C105362:RIF2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; C505160:Ogg1 protein, S cerevisiae