ミエオシスにおけるMLH1-MLH3エンドヌクレアスの調節

Elda Cannavo¹, Aurore Sanchez¹, Roopesh Anand¹

¹Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera italiana (USI), Bellinzona, Switzerland.

Nature

|August 21, 2020

まとめ

研究者らは微分化の過程で DNAの交差形成を促進するタンパク質複合体を特定しましたこの発見により,染色体間で遺伝物質が交換され,適切な細胞分裂と遺伝的多様性を確保することが明らかになった.

科学分野:

分子生物学
遺伝学
細胞生物学

背景:

ミエオシスには,同種の再結合によって修復されたプログラムされたDNAの断裂が含まれます.
MLH1-MLH3 (MutLγ) ヌクレアース経路は,メオティック再結合中間物質をクロスオーバーにバイアス的に処理するために不可欠です.
MutLγのプロクロスオーバー活動の正確なメカニズムは不明である.

研究の目的:

MutLγを含むプロクロスオーバー経路を生化学的に再構成し,特徴づけること.
メイオティッククロスオーバー形成におけるMSH4-MSH5 (MutSγ),EXO1,RFC,PCNAの役割を明らかにする.

主な方法:

MutLγ-MutSγ-EXO1-RFC-PCNA核酵素組の生化学的再構成
枝分かれした再結合中間体とホリデイ・ジャンクションのDNA分裂活性を測定する試験.
MutLγ-PCNAの相互作用が損なわれた酵母菌株におけるクロスオーバー形成の欠陥の分析

主要な成果:

ヒトMSH4-MSH5 (MutSγ) は再結合中間物質を結合し,MutLγアンサンブルを安定させる.
MutSγは,EXO1,RFC,PCNAによってさらに強化された,MutLγエンドヌクレアスの活性を直接刺激する.
再構成されたヌクレアースエンサンブルは,ホリデイ・ジャンクションに隣接するDNAを好ましく切り取ります.
酵母におけるMutLγ-PCNA相互作用の障害は,クロスオーバー形成の欠陥につながる.

結論:

MutLγ-MutSγ-EXO1-RFC-PCNA複合体は,メオティッククロスオーバーを促進する核酵素集合体として作用する.
複合体はおそらくDNAを切り離して再結合中間物質を処理し,共因子の分布は分裂をバイアスする可能性がある.
このメカニズムは,メオティック再結合中間物のクロスオーバー特異的な処理を説明する.

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