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dc.contributor.author de Siervi, Adriana
dc.contributor.author de Luca, Paola
dc.contributor.author Byun, Jung S.
dc.contributor.author Di, Li Jun
dc.contributor.author Fufa, Temesgen
dc.contributor.author Haggerty, Cynthia M.
dc.contributor.author Vazquez, Elba Susana
dc.contributor.author Moiola, Cristian Pablo
dc.contributor.author Longo, Dan L.
dc.contributor.author Gardner, Kevin
dc.date.available 2017-05-17T18:57:45Z
dc.date.issued 2010-01
dc.identifier.citation de Siervi, Adriana; de Luca, Paola; Byun, Jung S.; Di, Li Jun; Fufa, Temesgen; et al.; Transcriptional Autoregulation by BRCA1; American Association For Cancer Research; Cancer Research; 70; 2; 1-2010; 532-542
dc.identifier.issn 0008-5472
dc.identifier.uri http://hdl.handle.net/11336/16581
dc.description.abstract The BRCA1 gene product plays numerous roles in regulating genome integrity. Its role in assembling supermolecular complexes in response to DNA damage has been extensively studied; however, much less is understood about its role as a transcriptional coregulator. Loss or mutation is associated with hereditary breast and ovarian cancers, whereas altered expression occurs frequently in sporadic forms of breast cancer, suggesting that the control of BRCA1 transcription might be important to tumorigenesis. Here, we provide evidence of a striking linkage between the roles for BRCA1 as a transcriptional coregulator with control of its expression via an autoregulatory transcriptional loop. BRCA1 assembles with complexes containing E2F-1 and RB to form a repressive multicomponent transcriptional complex that inhibits BRCA1 promoter transcription. This complex is disrupted by genotoxic stress, resulting in the displacement of BRCA1 protein from the BRCA1 promoter and subsequent upregulation of BRCA1 transcription. Cells depleted of BRCA1 respond by upregulating BRCA1 transcripts, whereas cells overexpressing BRCA1 respond by downregulating BRCA1 transcripts. Tandem chromatin immmunoprecipitation studies show that BRCA1 is regulated by a dynamic coregulatory complex containing BRCA1, E2F1, and Rb at the BRCA1 promoter that is disrupted by DNA-damaging agents to increase its transcription. These results define a novel transcriptional mechanism of autoregulated homeostasis of BRCA1 that selectively titrates its levels to maintain genome integrity in response to genotoxic insult.
dc.format application/pdf
dc.language.iso eng
dc.publisher American Association For Cancer Research
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject BRCA1
dc.subject Transcripción
dc.subject Daño en el ADN
dc.subject Ciclo celular
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Transcriptional Autoregulation by BRCA1
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-05-11T20:57:29Z
dc.identifier.eissn 1538-7445
dc.journal.volume 70
dc.journal.number 2
dc.journal.pagination 532-542
dc.journal.pais Estados Unidos
dc.journal.ciudad Filadelfia
dc.description.fil Fil: de Siervi, Adriana. National Cancer Institute; Estados Unidos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: de Luca, Paola. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Byun, Jung S.. National Cancer Institute; Estados Unidos
dc.description.fil Fil: Di, Li Jun. National Cancer Institute; Estados Unidos
dc.description.fil Fil: Fufa, Temesgen. National Cancer Institute; Estados Unidos
dc.description.fil Fil: Haggerty, Cynthia M.. National Cancer Institute; Estados Unidos
dc.description.fil Fil: Vazquez, Elba Susana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Moiola, Cristian Pablo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Longo, Dan L.. National Institute on Aging; Estados Unidos
dc.description.fil Fil: Gardner, Kevin. National Cancer Institute; Estados Unidos
dc.journal.title Cancer Research
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952428/?tool=pubmed
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1158/0008-5472.CAN-09-1477
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/70/2/532


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)