Published online 5 August 1999 | Nature | doi:10.1038/news990805-7

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How DNA does the twist

Before a cell divides, its DNA condenses a thousandfold so that each chromosome is clumped together. Now a report in Cell [23 July 1999] offers an explanation of how a cell accomplishes this engineering triumph. The results provide a possible solution to the problem of how the DNA in each human cell (which, if stretched end-to-end, would measure about a metre) not only fits into the tiny cell nucleus but, when necessary, scrunches up still more.

DNA in a cell is a bit like a coiled telephone cord. Sometimes telephone cords get all tangled up in a bunch so that one portion of the cord is crossing over another bit. When this happens to DNA it is called supercoiling. If the coil happens to overlap itself in one direction, it is called a ‘positive supercoil’; if in the opposite direction, a ‘negative supercoil’.

During most of the life of a cell, its DNA is spread out in the nucleus. This allows the cellular machinery access to it in order to translate it into proteins. But when a cell is about to divide it makes a copy of its entire DNA, and then the chromosomes condense and line up in a row.

The first part of this bunching is helped along by a mass of proteins called histones, around which the DNA wraps like string around a yo-yo. But when it is wrapped around the histone the DNA is still about ten times as long as it needs to be. This is where the new research comes in. Nicholas Cozzarelli of the University of California, Berkeley, and colleagues show that this protein called 13S condensin can make DNA twist up into positive supercoils.

Researchers know that this protein somehow completes the job, but, until now, no one had any idea how. Unlike a phone cord, which, much to one’s irritation, sometimes seems to want to coil up spontaneously, winding up DNA in the same way takes a lot of energy. Cozzarelli’s group showed that 13S condensin gets its energy from ATP - the energy-generator of the cell (although they caution that the experiments were done in a test tube, not a cell). They also showed that condensin can do its thing only when the cell is getting ready to divide. At other times during the cell’s life, it doesn’t have this function.