DNA topology: nature’s headphone

cord problem

Bonnie Barrilleaux

Let’s get oriented

DNA is really long, and the nucleus is really

tiny

A single cell contains

six feet of DNA.

Ten cell nuclei = thickness of 1 human hair.

=

Shoving a six foot string into a 10 micron sack

You might think that it would all get tangled.

You’d be right.“The longer a string is, the more easily it gets

tangled.” –Captain Obvious

D.M. Raymer and D.E.Smith, “Spontaneous knotting of an agitated string”, PNAS 104:42, 2007

Yet somehow, DNA stays organized

Different chromosomes are confined to discrete territories.

Here, chromosomes 2 and 9 are stained green and red.

DNA is stained blue.

Mayer et al., BMC Cell Biology 2005, 6:44.

Spooling DNA onto histones

Histones are positively charged proteins.

DNA winds onto them – step one, of many layers of winding.

Diagram by Thomas Splettstoesser

Local structure…DNA wraps around

histones to form nucleosomes.

Nucleosomes line up to form 30 nanometer fibers.

…becomes larger-scale structure

DNA is further wound into chromatin fibers.

Chromosomes only look tidy when the cell is preparing to divide.

Most of the time they’re unpacked and much messier.

Chromosome domainsScaffold/Matrix

Attachment Regions: Specific regions of DNA attach to the inner surface of the nucleus.

This is still somewhat mysterious.

Each chromosome stays in its own zone.

Bolzer et al., (2005) PLOS Biol 3(5)

Things get tangled anyway

The entire chromosome has to unwind every time it gets copied.

Regions have to unwind to transcribe genes.

Topoisomerases to the rescue

Topoisomerases can cut DNA, untangle it, and stick it back together.

How the magic happens

Putting it all togetherThe end result is

elegant, functional, and still somewhat of a mystery.

But it works!