Positive Feedback Loops that Drive Cell Decisions
Dividing is one of the trickiest things a cell has to do. The cell needs to faithfully copy its entire genome, with very few mistakes, and it needs to then divvy up those two genome copies equally among the two new cells that are created during division. Going through this process is a bit like going down a double black diamond ski run: once you set things in motion, there's no stopping until you get to the end.
In the case of cell division, there are two critical points of no return: at the decision to start replicating DNA, and when it's time to equally split up the chromosomes. A cell that's going to copy its genetic material had better be ready, with all the necessary supplies in hand, because once the copying process initiates, it's a bad idea to stop: a cell can't really do much with a half-replicated genome, and it's in danger of permanently ruining its genome. And it doesn't do you any good to successfully finish that copying process, only to misallocate what you've copied among the two daughter cells. Without the right chromosomes in each cell, there is only a slim chance of survival.
So how do cells make these critical decisions? Two papers in this week's issue of Nature argue that positive feedback plays a major role. You've probably experienced how painfully effective positive feedback when someone talks into a microphone placed to close a speaker: the sound gets transmitted from the speaker to the microphone, where it is amplified by the speaker and transmitted to the microphone again etc., until everyone in the audience is awake again. Positive feedback happens when the end result of a process goes back and initiates more of that process.
Researchers led by David Morgan, at UC San Francisco found that a positive feedback loop initiates chromosome separation. Once a chromosome is copied, the two copies stick together until it's time to part company and split one cell into two. If those chromosomes don't stick together, chances are at least one of them will get lost in the shuffle. Morgan's group found that the chromosomes split up rapidly because a positive feedback loop leads to the abrupt dissolution of the glue holding the pairs of chromosomes together.
At the other end of the cell cycle, a group at the Rockefeller University, led by Fred Cross and Eric Siggia, looked at the decision to start replicating DNA. It turns out that there is a positive feedback loop there to. Once the cell decides that all systems are ready to fire, it moves ahead on all cylinders, thanks to a positive feedback loop that quickly lets the cell leave behind its pre-replication phase.
Much of molecular biology has been an attempt to figure out how the various parts of the cell works. But once you a fairly good functional parts list, like we do for cell division in the yeast model system (which is what these two papers studied), you can put things together and understand cellular processes more like an engineers, and less like Rube Goldberg (who, I'll admit, did have a good understanding of positive feedback loops.)
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