Your browser doesn't support javascript.
loading
DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells.
He, Yizhou Joseph; Meghani, Khyati; Caron, Marie-Christine; Yang, Chunyu; Ronato, Daryl A; Bian, Jie; Sharma, Anchal; Moore, Jessica; Niraj, Joshi; Detappe, Alexandre; Doench, John G; Legube, Gaelle; Root, David E; D'Andrea, Alan D; Drané, Pascal; De, Subhajyoti; Konstantinopoulos, Panagiotis A; Masson, Jean-Yves; Chowdhury, Dipanjan.
Afiliación
  • He YJ; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Meghani K; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Caron MC; Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Axis, Québec City, Québec, Canada.
  • Yang C; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec City, Québec, Canada.
  • Ronato DA; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Bian J; Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Axis, Québec City, Québec, Canada.
  • Sharma A; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec City, Québec, Canada.
  • Moore J; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Niraj J; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
  • Detappe A; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Doench JG; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Legube G; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Root DE; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • D'Andrea AD; LBCMCP, Centre de Biologie Integrative (CBI), CNRS, Université de Toulouse, UT3, Toulouse, France.
  • Drané P; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • De S; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Konstantinopoulos PA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Masson JY; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Chowdhury D; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Nature ; 563(7732): 522-526, 2018 11.
Article en En | MEDLINE | ID: mdl-30464262
Limited DNA end resection is the key to impaired homologous recombination in BRCA1-mutant cancer cells. Here, using a loss-of-function CRISPR screen, we identify DYNLL1 as an inhibitor of DNA end resection. The loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and inhibitors of poly(ADP-ribose) polymerase. Low BRCA1 expression correlates with increased chromosomal aberrations in primary ovarian carcinomas, and the junction sequences of somatic structural variants indicate diminished homologous recombination. Concurrent decreases in DYNLL1 expression in carcinomas with low BRCA1 expression reduced genomic alterations and increased homology at lesions. In cells, DYNLL1 limits nucleolytic degradation of DNA ends by associating with the DNA end-resection machinery (MRN complex, BLM helicase and DNA2 endonuclease). In vitro, DYNLL1 binds directly to MRE11 to limit its end-resection activity. Therefore, we infer that DYNLL1 is an important anti-resection factor that influences genomic stability and responses to DNA-damaging chemotherapy.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Proteína BRCA1 / Genes BRCA1 / Dineínas Citoplasmáticas / Reparación del ADN por Recombinación / Proteína Homóloga de MRE11 Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Nature Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Proteína BRCA1 / Genes BRCA1 / Dineínas Citoplasmáticas / Reparación del ADN por Recombinación / Proteína Homóloga de MRE11 Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Nature Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido