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The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during metaphase of mitosis or meiosis that prevents the separation of the duplicated chromosomes until each chromosome is properly attached to the ...
The mitotic spindle checkpoint occurs at the point in metaphase where all the chromosomes should/have aligned at the mitotic plate and be under bipolar tension. The tension created by this bipolar attachment is what is sensed, which initiates the anaphase entry.
Cells with a defective G 2-M checkpoint will undergo apoptosis or death after cell division if they enter the M phase before repairing their DNA. [1] The defining biochemical feature of this checkpoint is the activation of M-phase cyclin-CDK complexes, which phosphorylate proteins that promote spindle assembly and bring the cell to metaphase. [2]
The mitotic spindle checkpoint verifies that all the chromosomes are aligned properly on the metaphase plate and prevents premature entry into anaphase. Chromosomes lined up on the metaphase plate. Two views with the metaphase plate rotated 60°. Stages of early mitosis in a vertebrate cell with micrographs of chromatids
A series of biochemical switches control transitions between and within the various phases of the cell cycle.The cell cycle is a series of complex, ordered, sequential events that control how a single cell divides into two cells, and involves several different phases.
Pharmacologically bypassing the G2/M checkpoint via inhibition of Chk1 has been shown to enhance cytotoxicity of other chemotherapy drugs. Bypassing the checkpoint leads to the rapid accumulation of deleterious mutations, which is thought to drive the cancerous cells into apoptosis .
The spindle checkpoint system is a regulatory system that restrains progression through the metaphase-to-anaphase transition. The Mad2 gene was first identified in the yeast S. cerevisiae in a screen for genes which when mutated would confer sensitivity to microtubule poisons. [ 1 ]
Role in cancer: Cyclin-dependent kinase inhibitor (CKI) mutants are frequent in human cancers. The function of CKI is to stop cell growth when there are mistakes due to DNA damage. Once a cell is stopped at a checkpoint due to DNA damage, either the damage is repaired or the cell is induced to perform apoptosis. [9]