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R-loop-dependent promoter-proximal termination ensures genome stability.
Xu, Congling; Li, Chengyu; Chen, Jiwei; Xiong, Yan; Qiao, Zhibin; Fan, Pengyu; Li, Conghui; Ma, Shuangyu; Liu, Jin; Song, Aixia; Tao, Bolin; Xu, Tao; Xu, Wei; Chi, Yayun; Xue, Jingyan; Wang, Pu; Ye, Dan; Gu, Hongzhou; Zhang, Peng; Wang, Qiong; Xiao, Ruijing; Cheng, Jingdong; Zheng, Hai; Yu, Xiaoli; Zhang, Zhen; Wu, Jiong; Liang, Kaiwei; Liu, Yan-Jun; Lu, Huasong; Chen, Fei Xavier.
Afiliação
  • Xu C; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Li C; Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
  • Chen J; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Xiong Y; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Qiao Z; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Fan P; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Li C; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Ma S; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • Liu J; Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
  • Song A; Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Tao B; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Xu T; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Xu W; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Chi Y; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.
  • Xue J; Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
  • Wang P; Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Ye D; Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Gu H; Huashan Hospital, Fudan University, Shanghai Key Laboratory of Medical Epigenetics, Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
  • Zhang P; Huashan Hospital, Fudan University, Shanghai Key Laboratory of Medical Epigenetics, Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
  • Wang Q; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Xiao R; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • Cheng J; Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zheng H; Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
  • Yu X; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Zhang Z; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
  • Wu J; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Liang K; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Liu YJ; Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Lu H; Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
  • Chen FX; Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
Nature ; 621(7979): 610-619, 2023 Sep.
Article em En | MEDLINE | ID: mdl-37557913
ABSTRACT
The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regiões Promotoras Genéticas / Instabilidade Genômica / Terminação da Transcrição Genética / Estruturas R-Loop Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regiões Promotoras Genéticas / Instabilidade Genômica / Terminação da Transcrição Genética / Estruturas R-Loop Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China