Significance of Error-avoiding Mechanisms for Oxidative DNA Damage in Carcinogenesis

Autor: Tsuzuki, Teruhisa, Isoda, Takuro, Piao, J, Yamauchi, Kazumi, Egashira, Akinori, Sakamoto, Katsumi, Kura, Shinobu, Nakabeppu, Yusaku, Nakatsu, Yoshimichi
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: 9th European Biological Inorganic Chemistry Conference : EUROBIC 9 : 2-6 September, 2008 Wroclaw, Poland. :7-14
Popis: Oxygen radicals are produced through normal cellular metabolism, and formation of such radicals is further enhanced by ionizing radiation and by various chemicals. Among various classes of oxidative DNA damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is the most abundant, and appears to play important roles in mutagenesis and carcinogenesis. We have focused on following the two enzymes. MTH1 protein hydrolyzes 8-oxo-dGTP to monophosphate in the nucleotide pool, thereby preventing occurrence of transversion mutations. On the other hand, MUTYH protein, having adenine/2-hydroxyadenine DNA glycosylase activity, is expected to prevent G:C to T:A transversions, by excising adenine from G:A mismatches induced by 8-oxoG and 2-OH-A. To analyze the function of the mammalian MTH1 and MUTYH proteins in vivo, we established gene-knockout mice for these two enzymes, and investigated spontaneous tumorigenesis as well as mutagenesis.
Databáze: OpenAIRE