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| Paviolo,Natalia Soledad; Vega,María Belén de la; Pansa,María Florencia; García,Iris Alejandra; Calzetta,Nicolás Luis; Soria,Gastón; Gottifredi,Vanesa. |
| Abstract The 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.... |
| Tipo: Info:eu-repo/semantics/article |
Palavras-chave: GammaH2AX; Alternative end joining; Non-homologous end joining; Homologous recombination; PARP. |
| Ano: 2020 |
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000200303 |
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