Odd chromosome movement and inaccurate chromosome distribution in
mitosis and meiosis after treatment with protein kinase inhibitors
In this paper the authors investigated errors in
chromosome orientation from grasshopper spermatocytes treated with the
protein kinase inhibitor Genistein.
Odd chromosome movement and inaccurate chromosome distribution in
mitosis and meiosis after treatment with protein kinase inhibitors.
Nicklas RB, Krawitz LE, Ward SC
J Cell Sci 1993 Apr 104 ( Pt 4) 961-73
Abstract
Errors in chromosome orientation in mitosis and meiosis are
inevitable, but normally they are quickly corrected.
We find that such errors usually are not corrected in cells treated
with protein kinase inhibitors. Highly inaccurate chromosome
distribution is the result.
When grasshopper spermatocytes were treated with the kinase
inhibitor 6-dimethylaminopurine (DMAP), 84% of maloriented chromosomes
failed to reorient; in anaphase, both partner chromosomes were
distributed to the same daughter cell. These chromosomes were observed
for a total of over 60 h, and not a single reorientation was seen. In
contrast, in untreated cells, maloriented chromosomes invariably
reoriented, and quickly: in 10 min, on average. A second protein kinase
inhibitor, genistein, had exactly the same effect as DMAP.
DMAP affected PtK1 cells in mitosis as it did spermatocytes in
meiosis: improper chromosome orientations persisted, leading to
frequent errors in distribution. We micromanipulated chromosomes in
spermatocytes treated with DMAP to learn why maloriented chromosomes
often fail to reorient.
Reorientation requires the loss of improper microtubule attachments
and the acquisition of new, properly directed kinetochore microtubules.
Micromanipulation experiments disclose that neither the loss of old nor
the acquisition of new microtubules is sufficiently affected by DMAP to
account for the indefinite persistence of malorientations.
Drug treatment causes a novel form of chromosome movement in which
one kinetochore moves toward another kinetochore. Two kinetochores in
the same chromosome or in different chromosomes can participate,
producing varied, dance-like movements executed by one or two
chromosomes. These kinetochore-kinetochore interactions evidently are
at the expense of kinetochore-spindle interactions.
We propose that malorientations persist in treated cells because the
kinetochores have numerous, short microtubules with a free end that can
be captured by a second kinetochore. Kinetochores capture each other's
kinetochore microtubules, leaving too few sites available for the
efficient capture of spindle microtubules.
Since the efficient capture of spindle microtubules is essential for
the correction of errors, failure of capture allows malorientations to
persist. Whether the effects of DMAP actually are due to protein kinase
inhibition remains to be seen.
In any case, DMAP reveals interactions of one kinetochore with
another, which, though ordinarily suppressed, have implications for
normal mitosis.
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