MAD2 BUBr1 issue molecular cancerology term paper for cell cycle 551
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The Mad2/BubR1 Issue
Nature vol 406 Cortez &eledge Conducting the mitotic symphony
Checkpoint mechanisms guide the Cell Cycle progression and ensure the integrity of the genome and the fidelity of chromosome segregation.
What we r sure of is that in mitosis , the spindle assembly checkpoint delays anaphase initiation until all the chromosomes are aligned at the metaphase plate , thereby ensuring the fidelity of sister chromatid separation .
This process monitors both the attachment of kinetochores to the mitotic spindle and the tension exerted on the kinetochores by the microtubules (Skoufias et al 2001 j.cell.biol 154)
The presence of one unattached kinetochore activates the spindle assembly checkpoint and prevents sister chromatid separation , anaphase initiation and loss of Cdc2 kinas activity , and so provides additional time for kinetochores to be captured by the mitotic spindle and for tension to be established at the kinetochores.
This checkpoint also functions in every cell cycle in the normal timing of anaphase initiation because unattached kinetochores are present in every prophase cell.
Thus this spindle assembly checkpoint is an intrinsic cell cycle quality control mechanism that acts to prevent aneuploidy due to unequal chromosome separation during mitosis .
The mitotic checkpoint can be activated experimentally by microtubule destabilizing drugs such as Vinblastine or Nocodazole.
By using such drugs , genetics studies in budding yeast have identified several components of the checkpoint pathway .
Mutations in any of these genes ( MAD1,2,3 -BUB1,2,3-MPS1) allow for the completion of
an aberrant mitosis in the presence of spindle defects and eventually lead to cell death...