首页|R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency

R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency

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DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability.While the impact of p53 deficiency on increasing DNA replication stress is known,the specific molecular mechanism un-derlying this phenomenon remains poorly understood.This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation,which is facilitated by the upregulation of RNR.Research has shown that p53 deficiency results in increased γH2AX expression and a higher mutation rate in the HPRT gene.Interestingly,these effects can be alleviated by rapamycin,an mTORC1 inhibitor.Additionally,rapa-mycin reduces the abundance of R-loop structures in p53KO cells,which is linked to mTORC1's regulation of ribonucleotide reductase(RNR)level.These findings suggest that p53 deficiency-induced DNA replication stress relies on mTORC1 activation,with the upregulation of RNR expression and R-loop formation.Overall,this study underscores the importance of R-loops in mTORC1 activation-dependent DNA replication stress triggered by p53 deficiency.

p53mTORC1DNA replication stressR loopsRNR

Xiaolei Li、Cheng Yang、Xiaohui Zhang、Feiyang Wang、Longhua Sun、Wei Zhang、Xinping Xu

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Jiangxi Provincial Key Laboratory of Respiratory Diseases,Jiangxi Institute of Respiratory Disease,Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,China

China-Japan Friendship Jiangxi Hospital,National Regional Center for Respiratory Medicine,Nanchang 330200,China

Jiangxi Medical College,First Clinical Medical College,Nanchang University,Nanchang 330006,China

Department of Respiratory and Critical Care Medicine,Renmin Hospital of Shangrao,Shangrao 334000,China

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2024

10.3724/abbs.2024188

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCD
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2024.56(12)