哺乳類SIRT6がない場合のゲノム不安定性および老化型フェノタイプ

Raul Mostoslavsky¹, Katrin F Chua, David B Lombard

¹Howard Hughes Medical Institute, The Children's Hospital, CBR Institute for Biomedical Research, Harvard University Medical School, Boston, MA 02115, USA.

Cell

|January 28, 2006

まとめ

SIRT6タンパク質は,マウスのDNA修復とゲノム安定性にとって極めて重要です. SIRT6の喪失は,未熟な老化のような症状とマウスの早期死亡につながる.

科学分野:

分子生物学は分子生物学である.
遺伝学遺伝学とは
バイオケミストリーバイオケミストリー

背景:

Sir2ヒストン脱酸化酵素は,酵母における重要な細胞過程を調節する.
哺乳類のSir2ホモログ (SIRT1-SIRT7) も同様の機能を持つ可能性がある.
哺乳類のSir2ホモログの特定の役割はほとんど不明である.

研究の目的:

哺乳類の細胞におけるSIRT6の機能を調査する.
マウスにおけるSIRT6のインビボの役割を決定する.
SIRT6とDNA修復,ゲノム安定性,そして老化との関係を調査する.

主な方法:

SIRT6の核性,クロマチン関連タンパク質としての特徴.
マウス細胞におけるDNA損傷耐性およびゲノム不安定性の評価.
SIRT6欠乏マウスのフェノタイプ分析.

主要な成果:

SIRT6はDNA損傷に対する耐性を促進し,ゲノム不安定性を抑制する.
SIRT6は塩基切除修復 (BER) に関わっています.
SIRT6欠乏したマウスは,成長遅延,リンパ減退,脂肪減少,主体縮症,代謝障害,早死を発症する.

結論:

SIRT6の機能は,正常なDNA修復を促進する.
SIRT6機能の喪失は,マウスの重度の発達異常と早死につながる.
SIRT6欠乏症は,老化に関連した変性プロセスの側面を再現します.

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