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In a well-known riddle, two blind men by chance enter a department store at the same time, go to the same counter, and both order five pairs of socks, each pair a different color. The sales clerk is so befuddled by this strange coincidence that he places all ten pairs (two black pairs, two blue pairs, two gray pairs, two brown pairs, and two green pairs) into a single shopping bag, gives the bag of socks to one blind man and an empty bag to the other. The two blind men happen to meet on the street outside, where they discover that one of their bags contains all ten pairs of socks. How do the blind men, without seeing and without any outside help, sort out the socks so that each man goes home with exactly five pairs of different colored socks? Can you come up with a solution to the riddle?

By an interesting coincidence, cells have the same dilemma as that of the blind men. Most organisms possess two sets of genetic information, one set inherited from each parent. Before cell division, the DNA in each chromosome replicates; after replication, there are two copies—called sister chromatids—of each chromosome. At the end of cell division, it is critical that each of the two new cells receives a complete copy of the genetic material, just as each blind man needs to go home with a complete set of socks.

The solution to the riddle is simple. Socks are sold as pairs; the two socks of a pair are typically connected by a thread. As a pair is removed from the bag, the men each grasp a different sock of the pair and pull in opposite directions. When the socks are pulled tight, one of the men can take a pocket knife and cut the thread connecting the pair. Each man then deposits his single sock in his own bag. At the end of the process, each man’s bag will contain exactly two black socks, two blue socks, two gray socks, two brown socks, and two green socks.*

Remarkably, cells employ a similar solution for separating their chromosomes into new daughter cells. As we will learn in this chapter, the replicated chromosomes line up at the center of a cell undergoing division and, like the socks in the riddle, the sister chromatids of each chromosome are pulled in opposite directions. Like the thread connecting two socks of a pair, a molecule called cohesin holds the sister chromatids together until severed by a molecular knife called separase. The two resulting chromosomes separate and the cell divides, ensuring that a complete set of chromosomes is deposited in each cell.

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In this analogy, the blind men and cells differ in one critical regard: if the blind men make a mistake, one man ends up with an extra sock and the other is a sock short, but no great harm results. The same cannot be said for human cells. Errors in chromosome separation, producing cells with too many or too few chromosomes, are frequently catastrophic, leading to cancer, miscarriage, or—in some cases—a child with severe handicaps.

* This analogy is adapted from K. Nasmyth. Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis. Annual Review of Genetics 35:673–745, 2001.