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ASTE1 promotes shieldin-complex-mediated DNA repair by attenuating end resection.
Zhao, Fei; Kim, Wootae; Gao, Huanyao; Liu, Chao; Zhang, Yong; Chen, Yuping; Deng, Min; Zhou, Qin; Huang, Jinzhou; Hu, Qi; Chen, Shih-Hsun; Nowsheen, Somaira; Kloeber, Jake A; Qin, Bo; Yin, Ping; Tu, Xinyi; Guo, Guijie; Qin, Sisi; Zhang, Chao; Gao, Ming; Luo, Kuntian; Liu, Yilun; Lou, Zhenkun; Yuan, Jian.
Afiliación
  • Zhao F; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Kim W; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Gao H; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
  • Liu C; Department of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
  • Zhang Y; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Chen Y; Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
  • Deng M; Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai, China.
  • Zhou Q; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Huang J; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Hu Q; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Chen SH; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
  • Nowsheen S; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
  • Kloeber JA; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
  • Qin B; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Yin P; Department of Dermatology, University of California San Diego, San Diego, CA, USA.
  • Tu X; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Guo G; Mayo Clinic Medical Scientist Training Program, Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
  • Qin S; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Zhang C; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Gao M; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Luo K; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Liu Y; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
  • Lou Z; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Yuan J; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Nat Cell Biol ; 23(8): 894-904, 2021 08.
Article en En | MEDLINE | ID: mdl-34354233
The shieldin complex functions as the downstream effector of 53BP1-RIF1 to promote DNA double-strand break end-joining by restricting end resection. The SHLD2 subunit binds to single-stranded DNA ends and blocks end resection through OB-fold domains. Besides blocking end resection, it is unclear how the shieldin complex processes SHLD2-bound single-stranded DNA and promotes non-homologous end-joining. Here, we identify a downstream effector of the shieldin complex, ASTE1, as a structure-specific DNA endonuclease that specifically cleaves single-stranded DNA and 3' overhang DNA. ASTE1 localizes to DNA damage sites in a shieldin-dependent manner. Loss of ASTE1 impairs non-homologous end-joining, leads to hyper-resection and causes defective immunoglobulin class switch recombination. ASTE1 deficiency also causes resistance to poly(ADP-ribose) polymerase inhibitors in BRCA1-deficient cells owing to restoration of homologous recombination. These findings suggest that ASTE1-mediated 3' single-stranded DNA end cleavage contributes to the control of DSB repair choice by 53BP1, RIF1 and shieldin.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas / Desoxirribonucleasa I / Reparación del ADN por Unión de Extremidades Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Cell Biol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas / Desoxirribonucleasa I / Reparación del ADN por Unión de Extremidades Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Cell Biol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido