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Restoration of Replication Fork Stability in BRCA1- and BRCA2-Deficient Cells by Inactivation of SNF2-Family Fork Remodelers.
Taglialatela, Angelo; Alvarez, Silvia; Leuzzi, Giuseppe; Sannino, Vincenzo; Ranjha, Lepakshi; Huang, Jen-Wei; Madubata, Chioma; Anand, Roopesh; Levy, Brynn; Rabadan, Raul; Cejka, Petr; Costanzo, Vincenzo; Ciccia, Alberto.
Afiliação
  • Taglialatela A; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Alvarez S; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Leuzzi G; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Sannino V; DNA Metabolism Laboratory, IFOM, FIRC Institute for Molecular Oncology, 20139 Milan, Italy.
  • Ranjha L; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Huang JW; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Madubata C; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
  • Anand R; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Levy B; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
  • Rabadan R; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
  • Cejka P; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
  • Costanzo V; DNA Metabolism Laboratory, IFOM, FIRC Institute for Molecular Oncology, 20139 Milan, Italy.
  • Ciccia A; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: ac3685@cumc.columbia.edu.
Mol Cell ; 68(2): 414-430.e8, 2017 Oct 19.
Article em En | MEDLINE | ID: mdl-29053959
To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells. In addition to SMARCAL1, other SNF2-family fork remodelers, including ZRANB3 and HLTF, cause nascent DNA degradation and genomic instability in BRCA1/2-deficient cells upon replication stress. Our observations indicate that nascent DNA degradation in BRCA1/2-deficient cells occurs as a consequence of MRE11-dependent nucleolytic processing of reversed forks generated by fork remodelers. These studies provide mechanistic insights into the processes that cause genome instability in BRCA1/2-deficient cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / DNA Helicases / Proteína BRCA2 / Ubiquitina-Proteína Ligases / Proteínas de Ligação a DNA / Quebras de DNA Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / DNA Helicases / Proteína BRCA2 / Ubiquitina-Proteína Ligases / Proteínas de Ligação a DNA / Quebras de DNA Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos