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ほ乳動物細胞におけるデオキシイノシンヌクレオチドによるゲノム不安定化機構とその防御システム
https://repo.qst.go.jp/records/64475
https://repo.qst.go.jp/records/64475ccbbf5a5-dd2e-46b1-987e-f448cc7a83b7
Item type | 会議発表用資料 / Presentation(1) | |||||
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公開日 | 2012-01-05 | |||||
タイトル | ||||||
タイトル | ほ乳動物細胞におけるデオキシイノシンヌクレオチドによるゲノム不安定化機構とその防御システム | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
資源タイプ | conference object | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
土本, 大介
× 土本, 大介× 猪山, 輝昭× アボルハッサニ, ノナ× 米嶋, 康臣× 作見, 邦彦× 塩見, 尚子× 森, 雅彦× 塩見, 忠博× 中別府, 雄作× 塩見 尚子× 森 雅彦× 塩見 忠博 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Inosine nucleotides, including ribo- and deoxyinosine nucleotides, are generated as products of oxidative deamination of adenine nucleotides as well as a precursor for purine nucleotide biosynthesis in living cells. These inosine nucleotides are converted to corresponding triphosphate forms by phosphorylation and can be incorporated into DNA or RNA. We have identified ITPA and NUDT16 as inosine nucleotides hydrolyzing enzymes in mammalian cells, and reported that ITPA deficiency results in perinatal lethality in mice with accumulation of inosine nucleotides, and that deficiency of either ITPA or NUDT16 causes growth arrest and genome instability in cultured mouse or human cells. To elucidate mechanisms of the cellular dysfunctions caused by deficiencies of ITPA or NUDT16 in human cells, we examined effects of simultaneous knockdown of several DNA repair enzymes in addition to ITPA or NUDT16, and found that knockdown of only one of mismatch repair genes suppresses the dysfunctions. Knockdown of ITPA or NUDT16 in mismatch repair deficient and proficient cells confirmed the results. We also found that simultaneous knockdown of two DNA excision repair enzymes exacerbated the dysfunctions, indicating that deoxyinosine incorporated into DNA causes the dysfunctions. The present study indicates that endogenous deoxyinosine nucleotides cause mismatch repair-dependent cell growth arrest and genome instability in human cells if they are not excluded from the nucleotide pool. | |||||
会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 第34回日本分子生物学会 | |||||
発表年月日 | ||||||
日付 | 2011-12-16 | |||||
日付タイプ | Issued |