LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 2 of total 2

Search options

  1. Article ; Online: Correction: Inhibitors of Rho kinases (ROCK) induce multiple mitotic defects and synthetic lethality in BRCA2-deficient cells.

    Martino, Julieta / Siri, Sebastián Omar / Calzetta, Nicolás Luis / Paviolo, Natalia Soledad / Garro, Cintia / Pansa, Maria F / Carbajosa, Sofía / Brown, Aaron C / Bocco, José Luis / Gloger, Israel / Drewes, Gerard / Madauss, Kevin P / Soria, Gastón / Gottifredi, Vanesa

    eLife

    2023  Volume 12

    Language English
    Publishing date 2023-11-14
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.94414
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Inhibitors of Rho kinases (ROCK) induce multiple mitotic defects and synthetic lethality in BRCA2-deficient cells.

    Martino, Julieta / Siri, Sebastián Omar / Calzetta, Nicolás Luis / Paviolo, Natalia Soledad / Garro, Cintia / Pansa, Maria F / Carbajosa, Sofía / Brown, Aaron C / Bocco, José Luis / Gloger, Israel / Drewes, Gerard / Madauss, Kevin P / Soria, Gastón / Gottifredi, Vanesa

    eLife

    2023  Volume 12

    Abstract: The trapping of Poly-ADP-ribose polymerase (PARP) on DNA caused by PARP inhibitors (PARPi) triggers acute DNA replication stress and synthetic lethality (SL) in BRCA2-deficient cells. Hence, DNA damage is accepted as a prerequisite for SL in BRCA2- ... ...

    Abstract The trapping of Poly-ADP-ribose polymerase (PARP) on DNA caused by PARP inhibitors (PARPi) triggers acute DNA replication stress and synthetic lethality (SL) in BRCA2-deficient cells. Hence, DNA damage is accepted as a prerequisite for SL in BRCA2-deficient cells. In contrast, here we show that inhibiting ROCK in BRCA2-deficient cells triggers SL independently from acute replication stress. Such SL is preceded by polyploidy and binucleation resulting from cytokinesis failure. Such initial mitosis abnormalities are followed by other M phase defects, including anaphase bridges and abnormal mitotic figures associated with multipolar spindles, supernumerary centrosomes and multinucleation. SL was also triggered by inhibiting Citron Rho-interacting kinase, another enzyme that, similarly to ROCK, regulates cytokinesis. Together, these observations demonstrate that cytokinesis failure triggers mitotic abnormalities and SL in BRCA2-deficient cells. Furthermore, the prevention of mitotic entry by depletion of Early mitotic inhibitor 1 (EMI1) augmented the survival of BRCA2-deficient cells treated with ROCK inhibitors, thus reinforcing the association between M phase and cell death in BRCA2-deficient cells. This novel SL differs from the one triggered by PARPi and uncovers mitosis as an Achilles heel of BRCA2-deficient cells.
    MeSH term(s) Anaphase ; DNA Damage ; Mitosis ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerases/metabolism ; Synthetic Lethal Mutations ; rho-Associated Kinases/antagonists & inhibitors ; BRCA2 Protein/genetics ; Humans
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; rho-Associated Kinases (EC 2.7.11.1) ; BRCA2 Protein
    Language English
    Publishing date 2023-04-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.80254
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top