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FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.
Huang, Min; Yao, Fuwen; Nie, Litong; Wang, Chao; Su, Dan; Zhang, Huimin; Li, Siting; Tang, Mengfan; Feng, Xu; Yu, Bin; Chen, Zhen; Wang, Shimin; Yin, Ling; Mou, Lisha; Hart, Traver; Chen, Junjie.
Afiliación
  • Huang M; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Yao F; Department of Hepatopancreatobiliary Surgery, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
  • Nie L; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wang C; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Su D; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhang H; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Li S; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Tang M; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Feng X; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Yu B; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chen Z; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wang S; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Yin L; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Mou L; Department of Hepatopancreatobiliary Surgery, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
  • Hart T; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chen J; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jchen8@mdanderson.org.
Mol Cell ; 83(15): 2810-2828.e6, 2023 08 03.
Article en En | MEDLINE | ID: mdl-37541219
DNA damage-activated signaling pathways are critical for coordinating multiple cellular processes, which must be tightly regulated to maintain genome stability. To provide a comprehensive and unbiased perspective of DNA damage response (DDR) signaling pathways, we performed 30 fluorescence-activated cell sorting (FACS)-based genome-wide CRISPR screens in human cell lines with antibodies recognizing distinct endogenous DNA damage signaling proteins to identify critical regulators involved in DDR. We discovered that proteasome-mediated processing is an early and prerequisite event for cells to trigger camptothecin- and etoposide-induced DDR signaling. Furthermore, we identified PRMT1 and PRMT5 as modulators that regulate ATM protein level. Moreover, we discovered that GNB1L is a key regulator of DDR signaling via its role as a co-chaperone specifically regulating PIKK proteins. Collectively, these screens offer a rich resource for further investigation of DDR, which may provide insight into strategies of targeting these DDR pathways to improve therapeutic outcomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos