title: Excision of 8-oxoguanine from methylated CpG dinucleotides by human 8-oxoguanine DNA glycosylase.
abstract: CpG dinucleotides are targets for epigenetic methylation, many of them bearing 5-methylcytosine (mCyt) in the human genome. Guanine in this context can be easily oxidized to 8-oxoguanine (oxoGua), which is repaired by 8-oxoguanine-DNA glycosylase (OGG1). We have studied how methylation affects the efficiency of oxoGua excision from damaged CpG dinucleotides. Methylation of the adjacent cytosine moderately decreased the oxoGua excision rate while methylation opposite oxoGua lowered the rate of product release. Cytosine methylation abolished stimulation of OGG1 by repair endonuclease APEX1. The OGG1 S326C polymorphic variant associated with lung cancer showed poorer base excision and lost sensitivity to the opposite-base methylation. The overall repair in the system reconstituted from purified proteins decreased for CpG with mCyt in the damaged strand.
authors: SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., Novosibirsk 630090, Russia.
authors: Rustem D
authors: RD
authors: Kasymov
authors: Inga R
authors: IR
authors: Grin
authors: Anton V
authors: AV
authors: Endutkin
authors: Serge L
authors: SL
authors: Smirnov
authors: Alexander A
authors: AA
authors: Ishchenko
authors: Murat K
authors: MK
authors: Saparbaev
authors: Dmitry O
authors: DO
authors: Zharkov
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D044503:5-Methylcytosine; D004247:DNA; D004257:DNA Polymerase II; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: 5-Methylcytosine; 8-Oxoguanine; DNA repair; Epigenetic methylation; OGG1