Mitotic checkpoints delay cell cycle progression in response to alterations of the mitotic apparatus, thus ensuring correct chromosome segregation. While unproper spindle orientation activates a Bub2/Bfa1-dependent checkpoint delaying exit from mitosis, the lack of bipolar kinetochore-microtubule attachment activates a signal transduction cascade, preventing both anaphase onset and mitotic exit by inhibiting the Cdc20/APC-mediated proteolysis of securin and inactivation of mitotic CDKs, respectively. Proteolysis of the securin Pds1 is necessary to liberate the separase Esp1, which then triggers sister chromatid separation, whereas inactivation of mitotic CDKs is a pre-requisite for exiting mitosis and starting a new round of DNA replication in the next cell cycle. In budding yeast, this checkpoint response involves the Mad1, 2, 3, Bub1 and Bub3 proteins, whose vertebrate counterparts localize at unattached kinetochores. Unlike mutations altering other kinetochore proteins, which result in mitotic checkpoint activation, the ndc10-1 mutation impairs not only kinetochore function, but also proper checkpoint response, indicating a role for Ndc10 in this process. Here we present evidence that Ndc10 is not part of the Bub2/Bfa1-dependent pathway, and its role in checkpoint response might be different also from that of the other Mad and Bub proteins. In fact, Ndc10, unlike other mitotic checkpoint proteins, is not required for the mitotic block induced by overexpression of the Mps1 protein kinase, which is implicated in mitotic checkpoint control. Furthermore, the mitotic exit delay caused by non-degradable Pds1, which does not require Mad and Bub proteins, depends on Ndc10 function. We propose that a pathway involving Ndc10 might monitor defects in the mitotic apparatus independently of the Mad and Bub proteins. Since the Esp1 separase is required for exiting mitosis in both ndc10-1 and mad2Δ nocodazole-treated cells, the two signal transduction cascades might in the end converge in the inactivation of Esp1.
Fraschini, R., Beretta, A., Lucchini, G., & Piatti, S. (2001). Role of the kinetochore protein Ndc10 in mitotic checkpoint activation. MOLECULAR GENETICS AND GENOMICS, 266, 115-125 [10.1007/s004380100533].
|Citazione:||Fraschini, R., Beretta, A., Lucchini, G., & Piatti, S. (2001). Role of the kinetochore protein Ndc10 in mitotic checkpoint activation. MOLECULAR GENETICS AND GENOMICS, 266, 115-125 [10.1007/s004380100533].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Titolo:||Role of the kinetochore protein Ndc10 in mitotic checkpoint activation|
|Autori:||Fraschini, R; Beretta, A; Lucchini, G; Piatti, S|
|Data di pubblicazione:||ago-2001|
|Rivista:||MOLECULAR GENETICS AND GENOMICS|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s004380100533|
|Appare nelle tipologie:||01 - Articolo su rivista|