酵母DNAポリメラーゼの [4Fe4S] クラスタに対するレドックス作用 δ

Phillip L Bartels¹, Joseph L Stodola², Peter M J Burgers²

¹Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.

Journal of the American Chemical Society

|November 23, 2017

まとめ

酵母DNAポリメラーゼデルタ (Pol δ) の鉄硫黄クラスターは酸化還元活性である. このクラスターはスイッチとして働き DNA合成を調節し複製のストレスに反応します

科学分野:

生物化学
分子生物学
バイオ物理学

背景:

ユカリオットB系DNAポリメラーゼのA [4Fe4S]クラスターは,活性複合体の形成に不可欠である.
Saccharomyces cerevisiaeのポリメラーゼデルタ (Pol δ) は,主要な遅延鎖DNAポリメラーゼである.

研究の目的:

Pol δにおける [4Fe4S] クラスタの酸化還元活性を調べる.
このクラスターがDNA合成を制御するスイッチとして機能するかどうか

主な方法:

レドックス活性を評価する電気化学的方法
DNA合成速度を測定する生化学的測定法
電気化学的酸化とPol δの還元
DNA結合アントラキノンによる光酸化

主要な成果:

DNAに結合したPol δは,生理学的潜在力において酸化還元活性を示す.
[4Fe4S]クラスタの電気化学的酸化はDNA合成を著しく遅らせます.
DNA合成の抑制は,クラスタの縮小によって逆転する.
光酸化により同様の結果が得られ,酸化還元スイッチのメカニズムが確認された.

結論:

Pol δ の [4Fe4S] クラスタは,酸化還元スイッチとして機能する.
このスイッチは,複製ストレスに対する迅速で可逆的な反応のメカニズムを提供します.
この酸化還元調節を理解することは,DNA複製の忠誠性とストレス反応を理解する鍵です.

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