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CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair.
Li, Feng; Sarangi, Prabha; Iyer, Divya Ramalingam; Feng, Hanrong; Moreau, Lisa; Nguyen, Huy; Clairmont, Connor; D'Andrea, Alan D.
Afiliación
  • Li F; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA.
  • Sarangi P; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA.
  • Iyer DR; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA.
  • Feng H; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA.
  • Moreau L; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA.
  • Nguyen H; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Clairmont C; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA.
  • D'Andrea AD; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Chief, Division of Genomic Stability and DNA Repair, Boston, MA 02215, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: alan_dandrea@dfci.harvard.edu
Cell Rep ; 40(9): 111297, 2022 08 30.
Article en En | MEDLINE | ID: mdl-36044844
A critical determinant of DNA repair pathway choice is REV7, an adaptor that binds to various DNA repair proteins through its C-terminal seatbelt domain. The REV7 seatbelt binds to either REV3, activating translesion synthesis, or to SHLD3, activating non-homologous end joining (NHEJ) repair. Recent studies have identified another REV7 seatbelt-binding protein, CHAMP1 (chromosome alignment-maintaining phosphoprotein 1), though its possible role in DNA repair is unknown. Here, we show that binding of CHAMP1 to REV7 activates homologous recombination (HR) repair. Mechanistically, CHAMP1 binds directly to REV7 and reduces the level of the Shieldin complex, causing an increase in double-strand break end resection. CHAMP1 also interacts with POGZ in a heterochromatin complex further promoting HR repair. Importantly, in human tumors, CHAMP1 overexpression promotes HR, confers poly (ADP-ribose) polymerase inhibitor resistance, and correlates with poor prognosis. Thus, by binding to either SHLD3 or CHAMP1 through its seatbelt, the REV7 protein can promote either NHEJ or HR repair, respectively.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Cromosómicas no Histona / Proteínas de Ciclo Celular / Reparación del ADN por Recombinación / Proteínas Mad2 Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Cromosómicas no Histona / Proteínas de Ciclo Celular / Reparación del ADN por Recombinación / Proteínas Mad2 Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos