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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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| Bonatto,D.; Revers,L.F.; Brendel,M.; Henriques,J.A.P.. |
| DNA double-strand breaks (DSBs) represent a major threat to the genomic stability of eukaryotic cells. DNA repair mechanisms such as non-homologous end joining (NHEJ) are responsible for the maintenance of eukaryotic genomes. Dysfunction of one or more of the many protein complexes that function in NHEJ can lead to sensitivity to DNA damaging agents, apoptosis, genomic instability, and severe combined immunodeficiency. One protein, Pso2p, was shown to participate in the repair of DSBs induced by DNA inter-strand cross-linking (ICL) agents such as cisplatin, nitrogen mustard or photo-activated bi-functional psoralens. The molecular function of Pso2p in DNA repair is unknown, but yeast and mammalian cell line mutants for PSO2 show the same cellular responses... |
| Tipo: Info:eu-repo/semantics/article |
Palavras-chave: Non-homologous end joining; Double-strand breaks; V(D)J; PSO2; Artemis; Saccharomyces cerevisiae. |
| Ano: 2005 |
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000300002 |
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