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Mechanism of genome instability mediated by human DNA polymerase mu misincorporation.
Guo, Miao; Wang, Yina; Tang, Yuyue; Chen, Zijing; Hou, Jinfeng; Dai, Jingli; Wang, Yudong; Wang, Liangyan; Xu, Hong; Tian, Bing; Hua, Yuejin; Zhao, Ye.
Afiliación
  • Guo M; Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • Wang Y; MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang University, Hangzhou, Zhejiang, China.
  • Tang Y; Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • Chen Z; MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang University, Hangzhou, Zhejiang, China.
  • Hou J; Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • Dai J; MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang University, Hangzhou, Zhejiang, China.
  • Wang Y; Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • Wang L; MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang University, Hangzhou, Zhejiang, China.
  • Xu H; Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • Tian B; MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang University, Hangzhou, Zhejiang, China.
  • Hua Y; Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • Zhao Y; MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang University, Hangzhou, Zhejiang, China.
Nat Commun ; 12(1): 3759, 2021 06 18.
Article en En | MEDLINE | ID: mdl-34145298
Pol µ is capable of performing gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Together with DNA ligase, misincorporation of dGTP opposite the templating T by Pol µ results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinetics of Pol µ substituting dGTP for dATP on gapped DNA substrates containing templating T were determined and compared. Pol µ is highly mutagenic on a 2-nt gapped DNA substrate, with T:dGTP base pairing at the 3' end of the gap. Two residues (Lys438 and Gln441) interact with T:dGTP and fine tune the active site microenvironments. The in-crystal misincorporation reaction of Pol µ revealed an unexpected second dGTP in the active site, suggesting its potential mutagenic role among human X family polymerases in NHEJ.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Disparidad de Par Base / Inestabilidad Genómica / ADN Polimerasa Dirigida por ADN / Reparación del ADN por Unión de Extremidades Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Disparidad de Par Base / Inestabilidad Genómica / ADN Polimerasa Dirigida por ADN / Reparación del ADN por Unión de Extremidades Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido