Any sailor worth her salt knows how to tie a bowline, with the trailing edge of the rope tucked underneath to make a knot. Healthy cells, it seems, perform a similar trick with the DNA at the ends of their chromosomes. In today's Cell, researchers report that the DNA on the end of human and mouse chromosomes forms a loop, with the exposed end tucked back into the DNA strand. This arrangement may help explain how a cell can tell the difference between broken DNA and normal chromosome ends.
At the end of each chromosome is a stretch of DNA and proteins called the telomere, which helps keep the chromosome from fraying during replication, like caps on shoelaces. Most people had pictured telomeres as linear stretches of DNA--perhaps sheathed by proteins. To explore how some of those associated proteins work, molecular biologists Jack Griffith and Titia de Lange created artificial telomeres, added the proteins, and examined the result under an electron microscope. To their surprise, they found lasso-shaped DNA loops, with the telomere end woven back into a particular section of DNA and several proteins holding the end in place.
To see if this knot occurs in real cells, the team painstakingly isolated telomeres from mouse and human cells--including some from Griffith's own blood. When they examined the telomeres, they again found loops--smaller ones in cells with short telomeres, and larger ones in cells with long telomeres. Although researchers have been studying telomeres for decades, no one had ever isolated them for examination under an electron microscope. (The telomeres are a minuscule part of the 2 meters of DNA in a typical cell.)
Griffith, De Lange, and their colleagues say the loops might shield the chromosome ends from the cell's DNA repair machinery, which searches out loose ends of DNA. The researchers are not yet sure how widespread telomere loops are--previous studies suggest that certain single-celled organisms may have proteins that bind tightly to telomere ends and might prevent the loops from forming. However, says biochemist Thomas Cech of the University of Colorado, knowing the structure of telomeres in mammals "is wonderful and important.... It's the starting point for properly framing your ideas about their function."