dc.creatorPaviolo, Natalia Soledad
dc.creatorde la Vega Páez, María Belén
dc.creatorPansa, Maria Florencia
dc.creatorGarcía, Iris Alejandra
dc.creatorCalzetta, Nicolás Luis
dc.creatorSoria, Gastón
dc.creatorGottifredi, Vanesa
dc.date.accessioned2021-04-19T19:07:39Z
dc.date.accessioned2022-10-15T00:35:57Z
dc.date.available2021-04-19T19:07:39Z
dc.date.available2022-10-15T00:35:57Z
dc.date.created2021-04-19T19:07:39Z
dc.date.issued2019-12-13
dc.identifierPaviolo, Natalia Soledad; de la Vega Páez, María Belén; Pansa, Maria Florencia; García, Iris Alejandra; Calzetta, Nicolás Luis; et al.; Persistent double strand break accumulation does not precede cell death in an olaparib-sensitive BRCA-deficient colorectal cancer cell model; Sociedade Brasileira de Genética; Genetics and Molecular Biology; 43; 1; 13-12-2019; 1-12
dc.identifier1415-4757
dc.identifierhttp://hdl.handle.net/11336/130374
dc.identifier1678-4685
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4325424
dc.description.abstractThe poly (adenosine diphosphate (ADP)-ribosyl) polymerase inhibitors (PARPi) selectively kill cancer cells with BRCA1 or BRCA2 (BRCA)-mutations. It has been proposed that cell death induction after PARPi depends on unrepaired double strand breaks (DSBs) that accumulate due to the homologous recombination deficiency of BRCA-mutated cells. Such accumulation of DSBs is inferred mainly from the high levels of DNA damage markers like phosphorylated histone H2AX. Herein, we developed a model of isogenic cell lines to show that depletion of BRCA causes PARPi-triggered cell death, replication stress (phosphorylated-H2AX and 53BP1 foci), and genomic instability. However, persistent DSBs accumulation was not detected under the same experimental conditions. Hence, at least in this cellular model, the trigger for cell death in PARPi-treated BRCA-depleted samples is not the accumulation of unrepaired DSBs. Instead, cell death better correlates with a rapid and aberrant resolution of DSBs by error-prone pathways that leads to severe chromosomic aberrations. Therefore, our results suggest that in PARPi-treated BRCA-deficient cells, chromosome aberrations may dually trigger both genomic instability and cell death.
dc.languageeng
dc.publisherSociedade Brasileira de Genética
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000200303&tlng=en
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1590/1678-4685-gmb-2019-0070
dc.rightshttps://creativecommons.org/licenses/by/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectALTERNATIVE END JOINING
dc.subjectGAMMAH2AX
dc.subjectHOMOLOGOUS RECOMBINATION
dc.subjectNON-HOMOLOGOUS END JOINING
dc.subjectPARP
dc.titlePersistent double strand break accumulation does not precede cell death in an olaparib-sensitive BRCA-deficient colorectal cancer cell model
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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