ヒトNEIL3の遺伝子発現はエピジェネティックに似た酸化性DNA変異によって調節される
Aaron M Fleming1, Judy Zhu1, Shereen A Howpay Manage1
1Department of Chemistry , University of Utah , Salt Lake City , Utah 84112-0850 , United States.
Journal of the American Chemical Society
|June 27, 2019
まとめ
NEIL3 DNA 修復遺伝子
科学分野:
- ゲノミクス
- DNA 修復
- エピジェネティクス
背景:
- 酸化性および炎症性ストレスはNEIL3遺伝子発現を誘導する.
- グアニン (G) を8-オクソ-7,8-ジヒドログアニン (OG) に酸化することは,ストレス中に発生する.
- NEIL3のG豊富なプロモーター要素は,潜在的なG四重複形成シーケンス (PQS) である.
研究 の 目的:
- 酸化ストレス中の遺伝子調節におけるNEIL3 PQSの役割を調査する.
- OGの形成と修復を含むNEIL3の活性化のメカニズムを探求する.
- NEIL3 PQSが酸化還元感受性規制要素として作用するかどうかを判断する.
主な方法:
- 熱力学と化学分析を用いたインビトロ試験
- DNA修復プロセスを調べるセルロースtudies.
- 配列保存のための哺乳類ゲノムのバイオ情報分析.
主要な成果:
- NEIL3 PQSにおけるOG形成は,OGG1による基礎切除修復を誘発し,基礎部位 (AP) を形成する.
- APサイトはDNAを不安定化し,PQS内のG四重複 (G4) 折りたたみを促進する.
- APE1は,G4の文脈でAPサイトを弱く切断し,トランスクリプショントランザクティベータとして作用することを可能にします.
結論:
- NEIL3 PQSは酸化還元スイッチとして機能し,OG改変によってNEIL3発現を調節する.
- このメカニズムにより,細胞は酸化ストレス中に変異性DNA損傷に反応します.
- 哺乳類のゲノムにわたって保存されたNEIL3 PQSは,この調節経路の進化的選択を示唆する.
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