Rogers, E., Bishop, J. D., Waddle, J. A., Schumacher, J. M. & Lin, R. The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis.
At the onset of anaphase, the release of chromosome cohesion is triggered by the cysteine protease, separase, which is also known as Extra Spindle Poles 1 (ESP1) from the original mutant of yeast [10], [11], [12], [13], [14].
Implementation of all three tests developed in this study, including source code, will be made available as part of the next release of our chromosome X-Wide Analysis tool-Set, whish is freely available for download from http://keinanlab.cb.bscb.cornell.edu/content/tools-data.
After these genetic swaps occur, the cohesin complexes are then selectively removed by different mechanisms, first to release the pairs of chromosomes and then the sister chromatids.
Two of the most dire consequences of premature release of TopoIIα from chromosomes by overexpressed geminin, especially before it religates the chromosomes are (1) low efficacy of TopoIIα drugs, for example, doxorubicin or etoposide; and (2) production of damaged chromosomes.
This triggers premature release of TopoIIα from chromosomes, which we propose induces aneuploidy in HME cells, since chromosome breakage generated through this mechanism were not sensed and/or repaired and the cell cycle was not arrested.
The second step takes place between late prophase and early prometaphase [ 85] and coincides with the release of cohesin from chromosomes through the action of the "prophase pathway".
Taken together, these data show that geminin overexpression triggers DNA damage, most likely by triggering premature release of TopoIIα from chromosomes before it religates DNA.
Given that cleavage of Scc1 will result in opening of the ring, it is easy to envisage why this causes the release of cohesin from chromosomes (Gruber et al. 2003).
In geminin-overexpressing cells, this could be accelerated by the fact that geminin recruits more of the enzymes and/or recruits them earlier to TopoIIα, thus leading to premature deSUMOylation and release of TopoIIα from chromosomes before the ligation step.
