DNA損傷後のG2停止を維持するためにp53とp21の要件

F Bunz¹, A Dutriaux, C Lengauer

¹The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.

Science (New York, N.Y.)

|November 20, 1998

まとめ

p53およびp21タンパク質は,DNA損傷後のG2細胞サイクルチェックポイントの維持に不可欠です. 機能的なp53またはp21がなければ,細胞は適切に停止できず,細胞分裂のエラーにつながります.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
遺伝学遺伝学とは

背景:

DNA損傷は,DNA修復を可能にするためにG2段階で細胞サイクル停止を誘発します.
腫瘍抑制タンパク質p53とその下流ターゲットであるp21は,細胞サイクルチェックポイントの重要な調節因子である.

研究の目的:

DNA損傷後のG2細胞サイクル停止を維持するp53とp21の役割を調査する.
人間の細胞における適切なG2チェックポイント機能のためにp53とp21の必要性を決定する.

主な方法:

人間の細胞におけるp53とp21の遺伝子破壊を利用する.
ガンマ放射線を用いてDNAの損傷を誘導する.
細胞形態学とDNA含有量の観察を通じて,細胞サイクル進行と細胞運動を分析する.

主要な成果:

持続的なG2停止は,p21.p21を活性化するp53の存在と転写活動に依存していた.
p53またはp21遺伝子の破壊は,DNAの損傷にもかかわらず,早すぎるミトーシスへの入り口をもたらしました.
機能的なp53またはp21が欠けている細胞は,適切な停止ではなく,失敗したサイトキネシスによるG2DNA含有を示した.

結論:

p53-p21経路は,DNA損傷後のヒト細胞のG2チェックポイントを維持するために不可欠です.
p53とp21は異常細胞分裂を防止し,ゲノム安定性を確保するために重要である.

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