A Conversation with Kerry Bloom.

Abstract

Dr. Bloom: The chromosome, in the public domain right now, is “the sequence.” Of course, there’s much more in the chromosome than the DNA sequence. That’s going to be the challenge for us moving forward: How do you store information? How do you propagate information beyond just the sequence of nucleic acids? Scientists have watched chromosomes move for hundreds of years, and it’s a ballet. They do this beautiful movement back and forth, literally dancing around each other until they finally all line up—I use that word loosely —and then go to what will be daughter cells. The accuracy that they must achieve to segregate all 46 chromosomes roughly 10 trillion times for all the cells in our body is beyond anything that’s ever been man-made. To get to your explicit question, they achieve that accuracy by building a spring between the twomicrotubule attachment sites. However, they don’t count chromosomes. You could have imagined a mechanism where they’re counting: “Is 1 lined up? Is 2 lined up?... Is 45 lined up? When 46 is lined up, let’s go.” They don’t do that. They build a little spring between the two microtubules from opposite spindle poles, and when that spring is under some tension, it quenches a checkpoint that is responsible for delaying the next phase of the cell cycle, when chromosomes segregate. If even one chromosome is still left behind (i.e., the spring is not under tension), that’ll suffice to delay the cell cycle. We’re interested in how that chromosome spring works. That region of the chromosome is called the centromere. There’s 6 feet of DNA in one cell. How do you take this very floppy molecule and build a molecular spring? That, basically, was our challenge.