BubR1 is a critical component of the spindle assembly checkpoint, the surveillance mechanism that helps maintain the high fidelity of mitotic chromosome segregation by preventing cells from initiating anaphase if one or more kinetochores are not attached to the spindle. BubR1 also helps promote the establishment of stable kinetochore-microtubule attachments during prometaphase. In this chapter, we review the structure, functions, and regulation of BubR1 in these "classical roles" at the kinetochore. We discuss its recruitment to kinetochores, its assembly into the inhibitor of anaphase progression, and the importance of its posttranslational modifications. We also consider the evidence for its participation in other roles beyond mitosis, such as the meiosis-specific processes of recombination and prophase arrest of the first meiotic division, the cellular response to DNA damage, and in the regulation of centrosome and basal body function. Finally, studies are presented linking BubR1 dysfunction or misregulation to aging and human disease, particularly cancer.
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http://dx.doi.org/10.1016/B978-0-12-407694-5.00006-7 | DOI Listing |
Andrology
December 2024
Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
Background: The establishment of kinetochore-microtubule attachment is essential for error-free chromosome alignment and segregation during cell division. Defects in chromosome alignment result in chromosome instability, birth defects, and infertility. Kinesin-7 CENP-E mediates kinetochore-microtubule capture, chromosome alignment, and spindle assembly checkpoint in somatic cells, however, mechanisms of CENP-E in germ cells remain poorly understood.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Laboratory of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address:
Ephexin proteins are guanine nucleotide exchange factors for the Rho GTPases. We reported that Ephexin4 regulates M-phase progression downstream of phosphorylated EphA2, a receptor-type tyrosine kinase, through RhoG activation; however, the regulation of Ephexin4 during M phase remains unknown. In this study, a novel Ephexin4 phosphorylation site was identified at Ser41, exclusively in M phase.
View Article and Find Full Text PDFMethods Mol Biol
November 2024
Endomembrane Structure and Function Research Group, Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK.
Cell division is a key cellular process that ensures the continuation of life on Earth. In order to protect the genetic integrity of organisms, cell division must happen accurately, ensuring each daughter cell receives a complete copy of the original genome. The accuracy of this process is, in part, preserved by various cell cycle checkpoints.
View Article and Find Full Text PDFCommun Biol
November 2024
The Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Semin Cancer Biol
November 2024
Biomedical Sciences Department, Creighton University School of Medicine, Omaha, NE, USA. Electronic address:
Aging is a significant risk factor for cancer which is due, in part, to heightened genomic instability. Mitotic surveillance proteins such as BubR1 play a pivotal role in ensuring accurate chromosomal segregation and preventing aneuploidy. BubR1 levels have been shown to naturally decline with age and its loss is associated with various age-related pathologies.
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