Mitotic spindle damage

It is possible to observe effects of organotin(lV) compounds exposure such as inhibition of cleavage of fertilized eggs, interference with the formation of the mitotic spindle, damages affecting chromosome structure, and electron-dense precipitate formation in organelles. 

Sallasidis K, Schmid E and Bauchinger M (1991). Mitotic spindle damage induced by 2-chlorobenzylidene malononitrile (CS) in V79 Chinese hamster cells examined by different staining of the spindle apparatus and chromosomes. MutatRes, 262, 263-266. 

In contrast to the DNA damage checkpoint, the mitotic spindle checkpoint is essential for cell viability. Dierefore, targeting kinases of the spindle checkpoint including Bubl, BubRl, and Mpsl might be a valid strategy for anticancer treatment. 

Available as a 0.5% gel or solution containing purified extract of the most active compound of podophyllin Arrests the formation of the mitotic spindle, prevents cell division, and may also induce damage in blood vessels within the warts... 

Taylor S S, McKeon F. Kinetochore localization of murine B ub 1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell 1997 89(5) 727-735. 

Damage to the mitotic spindle (B). The contractile proteins of the spindle apparatus must draw apart the replicated chromosomes before the cell can divide. This process is prevented by the so-called spindle poisons (see also colchicine, p. 326) that arrest mitosis at metaphase by disrupting the assembly into spindle threads of microtubuli. These consist of the proteins a-and p-tubulin. Surplus tubuli are broken down, enabling the tubulin subunits to be recycled. 

Another class of substrates comprises the anaphase inhibitors, e. g., the protein securin. Securin is an inhibitor of a protease named separase, which cleaves proteins responsible for sister chromatid cohesion in metaphase. Destruction of these inhibitors is necessary for triggering of sister chromatid separation and progression into anaphase. Because of its central function, the APC is part of several cell cycle checkpoints, e. g., a DNA damage checkpoint and the mitotic spindle checkpoint. 

EXAMPLE 8.9 There are a number of checkpoints in the cell cycle. Gj has a checkpoint that prevents progression into M phase unless replication of all chromosomal DNA is complete. The M phase checkpoint ensures that the chromosomes have been correctly attached to the mitotic spindle. Checkpoints in the G, and S phases lead to arrest of the cell cycle if damaged DNA is detected by the relevant protein complex. 

Malfunction of critical organelles or structures (e.g., faulty mitotic spindle) and/or DNA damage prompts checkpoints to activate cell cycle arrest and trigger apoptotic cell death cascades if the damage is not repcured. 

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