When cells divide
Studies of how chromosomes bind and release
may shed light on cancer and birth defects
Cells are dividing all the time, and that’s
a good thing. If they didn’t, our tissue and organs
couldn’t replenish themselves, and pretty soon
we’d be done for. But when cell division goes
wrong, it can have disastrous results, such as cancer
and birth defects.
Scientists in the lab of Whitehead Member and MIT professor
of biology Terry
Orr-Weaver have uncovered one of the primary mechanisms
governing cell division, publishing the
results earlier this year in the journal Developmental
Cell.
“This paper advances our understanding of how
the accurate partitioning of chromosomes is ensured
during cell division by defining the mechanisms controlling
a key protein in the
process, MEI-S332,” says Orr-Weaver.
Except for egg and sperm cells, all of the chromosomes
in our cells come in pairs. Half of each pair comes
from our mother, and the other half from our father.
When a cell divides to give birth to two daughter cells,
it must ensure that both new cells also contain a complete
maternal and complete paternal set of chromosomes.
"The failure of this glue-like protein to
function properly will result in cells with either
too many or too few chromosomes. Hence birth defects
or cancer."
Whitehead Postdoctoral
Researcher Astrid Clarke |
To do this, the cell first enters into an intermediate
stage where its number of chromosomes doubles, resulting
in a single cell that for a brief time contains all
the genetic material for two cells. During that time,
the chromosomes are paired and attached to each other—mother
to mother, father to father—by proteins that act
as a sort of glue.
When the time comes for cell division to complete,
the protein dissolves and releases the chromosomes from
each other, allowing them to separate into the daughter
cells. This protein-based “glue” is regulated
by the MEI-S332 protein discovered in the Orr-Weaver
lab and found in both fruit flies and mammals.
“The failure of this glue-like protein to function
properly will result in cells with either too many or
too few chromosomes,” says Astrid Clarke, a postdoctoral
researcher in the Orr-Weaver lab and lead author on
the paper. “Hence birth defects or cancer.”
Through studying how this protein functions in the
fruit fly, Clarke identified the precise chemical reaction
by which the protein binds and then releases the chromosomes
during this intermediate stage. The key finding was
that the protein releases the chromosomes from each
other by adding a phosphate to the binding point.
These findings are particularly significant given that
researchers have found that levels of MEI-S332 are higher
than normal in 90% of all breast cancers. According
to Clarke, this might mean that when there’s too
much of the protein, the chromosomes don’t separate
properly, or it might mean that the MEI-S332 gene is
mutated on the chromosomes. Either way, “there
definitely is a direct link between our protein and
cancer,” says Clarke.
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