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DSB repair pathway choice is regulated by recruitment of 53BP1 through cell cycle-dependent regulation of Sp1.
Swift, Michelle L; Beishline, Kate; Flashner, Samuel; Azizkhan-Clifford, Jane.
Afiliación
  • Swift ML; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA.
  • Beishline K; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA.
  • Flashner S; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA.
  • Azizkhan-Clifford J; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: jane.clifford@drexel.edu.
Cell Rep ; 34(11): 108840, 2021 03 16.
Article en En | MEDLINE | ID: mdl-33730584
Although many of the factors, epigenetic changes, and cell cycle stages that distinguish repair of double-strand breaks (DSBs) by homologous recombination (HR) from non-homologous end joining (NHEJ) are known, the underlying mechanisms that determine pathway choice are incompletely understood. Previously, we found that the transcription factor Sp1 is recruited to DSBs and is necessary for repair. Here, we demonstrate that Sp1 localizes to DSBs in G1 and is necessary for recruitment of the NHEJ repair factor, 53BP1. Phosphorylation of Sp1-S59 in early S phase evicts Sp1 and 53BP1 from the break site; inhibition of that phosphorylation results in 53BP1 and Sp1 remaining at DSBs in S phase cells, precluding BRCA1 binding and suppressing HR. Expression of Sp1-S59A increases sensitivity of BRCA1+/+ cells to poly (ADP-ribose) polymerase (PARP) inhibition similar to BRCA1 deficiency. These data demonstrate how Sp1 integrates the cell cycle and DSB repair pathway choice to favor NHEJ.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ciclo Celular / Factor de Transcripción Sp1 / Roturas del ADN de Doble Cadena / Reparación del ADN por Unión de Extremidades / Proteína 1 de Unión al Supresor Tumoral P53 Límite: Humans Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ciclo Celular / Factor de Transcripción Sp1 / Roturas del ADN de Doble Cadena / Reparación del ADN por Unión de Extremidades / Proteína 1 de Unión al Supresor Tumoral P53 Límite: Humans Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos