Biology Reference
In-Depth Information
Mad2
APC
Mad2*
Unattached spindle
Securin
Spindle
Chromatids
attached to each
other
FIGURE 22.4 Essential features of the spindle assembly check in the fission yeast, S. pombe. Signals generated by
unattached kinetochores of one chromatic pair can block anaphase separation even of another chromatid pairs that
is correctly bound to the spindle, so the whole cell has to wait until spindle attachment is complete. The * symbol
denotes activation of Mad. Facilitators of anaphase progression are coloured green and inhibitors are coloured pink.
from the metaphase to anaphase stages of mitosis is dependent, for example, on a signal that
verifies that all kinetochores have become properly attached to the mitotic spindle. Un-
attached kinetochores activate the diffusible protein Mad2, which inhibits the Anaphase
Promoting Complex of proteins. 15 Once all kinetochores are bound to the spindle, Mad2 acti-
vation ceases and, as already activated Mad2 remains active for only a short time, the
Anaphase Promoting Complex is freed of inhibition. It can therefore ubiquitinate and hence
destroy proteins that cause sister chromatids to be stuck together. The chromatids can there-
fore separate and anaphase can begin ( Figure 22.4 ).
Progression from G1 to S phase must be delayed until the cell has grown large enough,
something that depends on the availability of nutrients as well as on elapsed time. Acti-
vation of DNA synthesis requires the cyclin-dependent kinase, Cdc2, to be active. Cdc2 is
present at all stages of the cell cycle but it is active only when bound to a suitable cyclin.
The cyclin Cig2 activates cdc2, and Cig1 is produced in G1 some time before the G1-S tran-
sition takes place. 16 Precocious activation of cdc2 is prevented by the protein Rum1, which is
made during the preceding mitosis and remains in the cell. 17 Progression fromG1 to S there-
fore depends on inactivation of Rum1. Rum1 can be deactivated by the cyclin Puc1, which
forms a complex with cdc2 that phosphorylates Rum1 and targets it for destruction. Puc1 is
itself upregulated in response to an increase in cell size. 18 The net result is that progress
from G1 to S is blocked until a cell has reached sufficient size for this transition to be reason-
able. There are plenty more checkpoints, many of which use a variation on the cyclin/cdk
system described above. What they have in common, in S. pombe and similar unicells, is
that each depends only on sensors that determine whether the previous stage has been
completed.
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