The spindle checkpoint: a quality control mechanism which ensures accurate chromosome segregation

Abstract

The centromere defines where on a chromosome the kinetochores assemble. Kinetochores, large protein structures, mediate chromosome segregation during mitosis and meiosis by performing three key functions. Firstly, kinetochores attach chromosomes to the microtubule spindle apparatus. Secondly, kinetochores co-ordinate microtubule dynamics to allow chromosomes to move along the spindle. Lastly, kinetochores generate the 'wait' signal which prevents anaphase onset until all the chromosomes are correctly aligned on the spindle. This signal forms part of the spindle checkpoint mechanism, a highly conserved cell cycle checkpoint which maintains the accuracy of the chromosome segregation process. This article provides a brief historical overview before focusing on some of the outstanding issues and more recent developments in the field.

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

“…Expression of nondegradable cyclin B prevents the resumption of meiosis in a subset of activated oocytes, suggesting that Cdc2 must be inactivated in order for the arrest to be relieved (Swan and Schupbach, 2007). In addition, maintenance of the meiotic arrest requires tension created on the kinetochores, suggesting participation of the spindle checkpoint that indirectly regulates Cdc2 (reviewed by Taylor et al, 2004). However, maintenance of the meiotic arrest differs in at least one respect from the situation in vertebrates: while Mos is present and active in mature oocytes of Drosophila, it is not required for the maintenance of the metaphase I arrest, because this arrest is normal in dmos null mutant oocytes (Ivanovska et al, 2004).…”

The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer

“…3 Neoadjuvant chemotherapy drugs, such as cisplatin and paclitaxel, were designed to halt cell proliferation and destroy tumor cells mainly by interfering with DNA replication, affecting chromosome alignment and/or segregation and causing DNA damage, which leads to cell cycle arrest and apoptosis. 4 The Aurora kinase family participates in the regulation of the cell cycle in an ordered process. The over-expressions of Aurora A and B kinases have been observed in many types of human cancer, including cervical cancer, ovarian cancer, breast cancer, colorectal cancer, and gastric cancer.…”

Novelsfi1Alleles Uncover Additional Functions for Sfi1p in Bipolar Spindle Assembly and Function

“…The spindle checkpoint acts as a surveillance system and monitors kinetochore-microtubule interactions during mitosis (Musacchio and Hardwick, 2002;Cleveland et al, 2003;Taylor et al, 2004). It helps ensure that all sister chromatids are bioriented, with sisters attached to opposite spindle poles, before anaphase onset.…”