Advertisement

Topics

Checkpoint Proteins Bub1 and Bub3 Delay Anaphase Onset in Response to Low Tension Independent of Microtubule-Kinetochore Detachment.

08:00 EDT 9th April 2019 | BioPortfolio

Summary of "Checkpoint Proteins Bub1 and Bub3 Delay Anaphase Onset in Response to Low Tension Independent of Microtubule-Kinetochore Detachment."

The spindle assembly checkpoint (SAC) delays anaphase onset until sister chromosomes are bound to microtubules from opposite spindle poles. Only then can dynamic microtubules produce tension across sister kinetochores. The interdependence of kinetochore attachment and tension has proved challenging to understanding SAC mechanisms. Whether the SAC responds simply to kinetochore attachment or to tension status remains obscure. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relation between attachment and tension. We developed a Taxol-sensitive yeast model to reduce tension in fully assembled spindles. Our results show that low tension on bipolar-attached kinetochores delays anaphase onset, independent of detachment. The delay is transient relative to that imposed by unattached kinetochores. Furthermore, it is mediated by Bub1 and Bub3, but not Mad1, Mad2, and Mad3 (BubR1). Our results demonstrate that reduced tension delays anaphase onset via a signal that is temporally and mechanistically distinct from that produced by unattached kinetochores.

Affiliation

Journal Details

This article was published in the following journal.

Name: Cell reports
ISSN: 2211-1247
Pages: 416-428.e4

Links

DeepDyve research library

PubMed Articles [16869 Associated PubMed Articles listed on BioPortfolio]

Bub1 is not essential for the checkpoint response to unattached kinetochores in diploid human cells.

Error-free chromosome segregation during mitosis depends on a functional spindle assembly checkpoint (SAC). The SAC is a multi-component signalling system that is recruited to unattached or incorrectl...

Implications of alternative routes to APC/C inhibition by the mitotic checkpoint complex.

The mitotic checkpoint (also called spindle assembly checkpoint) is a signaling pathway that ensures faithful chromosome segregation. Mitotic checkpoint proteins inhibit the anaphase-promoting complex...

Spindly and Bub3 expression in oral cancer: prognostic and therapeutic implications.

Bub3 and Spindly are essential proteins required for the activation and inactivation of the spindle assembly checkpoint, respectively. Here, we explored the clinicopathological significance and the th...

Heat shock-induced mitotic arrest requires heat shock protein 105 for the activation of spindle assembly checkpoint.

Heat shock causes proteotoxic stress that induces various cellular responses, including delayed mitotic progression and the generation of an aberrant number of chromosomes. In this study, heat shock d...

Spindlin1 alters the metaphase to anaphase transition in meiosis I through regulation of BUB3 expression in porcine oocytes.

Spindlin 1 (SPIN1), which contains Tudor-like domains, regulates maternal transcripts via interaction with a messenger RNA (mRNA)-binding protein. SPIN1 is involved in tumorigenesis in somatic cells a...

Clinical Trials [6350 Associated Clinical Trials listed on BioPortfolio]

Resistance to Immunotherapy in Gastric Cancer

This project seeks to analyze and define the mechanism (s) involved in the resistance to checkpoint therapy in metastatic GC patients. The investigators propose the use of a Next-Generatio...

Reported Time Between Onset and Diagnosis of Alzheimer's Disease: Correlation With Objective Parameters

The early diagnosis of Alzheimer's disease is essential to enable patients to have access to the available treatments. However, there is a delay between the diagnosis and the onset of symp...

Personalizing Immune Checkpoint Inhibitor Therapy

This prospective, observational study will evaluate whether vitro testing of tumor tissue and white blood cells from patients with lung cancer who are being treated with immune checkpoint ...

Dose Ranging Study to Assess the Safety and Efficacy of SCV-07 for the Delay to Onset of Severe Oral Mucositis in Patients Receiving Chemoradiation Therapy for Head and Neck Cancer

Oral Mucositis (OM) is a painful and debilitating side effect of many of the drug or radiation regiments used to treat cancer. This study examines the investigational drug SCV-07 and it's...

Study Looking at the Recovery of New Onset Cardiomyopathy

This is a multi-center, prospective evaluation of left ventricular recovery on conventional therapy in patients with the recent onset of dilated cardiomyopathy. In some subjects with this ...

Medical and Biotech [MESH] Definitions

Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.

A serine/threonine-specific protein kinase which is encoded by the CHEK1 gene in humans. Checkpoint kinase 1 (also known as Chk1) coordinates DNA damage response and cell cycle checkpoint response. Under these conditions, activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death, to prevent damaged cells from progressing through the cell cycle.

Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.

Securin is involved in the control of the metaphase-anaphase transition during MITOSIS. It promotes the onset of anaphase by blocking SEPARASE function and preventing proteolysis of cohesin and separation of sister CHROMATIDS. Overexpression of securin is associated with NEOPLASTIC CELL TRANSFORMATION and tumor formation.

An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Searches Linking to this Article