LA JOLLA, CA -- When you dial 911 you expect rescuers to pull up at your front door, unload and get busy--not park the truck down the street and eat donuts.

It's the same for a cell--just before it divides, it recruits protein complexes that repair breakage that may have occurred along the linear DNA chains making up your 46 chromosomes. Without repair, damage caused by smoking, chemical mutagens, or radiation might be passed on to the next generation.

However, in 2005, investigators at the Salk Institute for Biological Studies observed that before cell division some of these cellular paramedics inexplicably idle at undamaged chromosome ends, known as telomeres. Apparently the telomeres' disheveled appearance --resembling that of broken DNA strands--raises a red flag.

Now, in a study published in the Nov. 17 issue of Cell, that same team led by Jan Karlseder, Ph.D, Hearst Endowment Assistant Professor in the Molecular and Cell Biology Laboratory, reveals why those repair crews are parked at the ends of chromosomes and in doing so answer fundamental questions about how chromosomal stability is maintained.

After the 2005 study, says Karlseder, "We formed a hypothesis that after telomeres replicate they need to be detected by the internal DNA damage machinery--otherwise they cannot form a protective structure, or chromosomal cap."

And that's exactly what the new study shows. Examining activity of telomeric and DNA repair proteins in cultured human cells, the investigators found that right before cell division cellular repair proteins (including one actually called the 9-1-1 complex) are recruited to exposed DNA ends. But rather than fixing what resembles a break, the repair crew, which first arrived at the scene, calls in a second conglomeration of repair proteins. This one, called the homologous recombination (HR) machinery, creates the protective structure.

"The HR machinery fixes any break in the gen
'"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute
16-Nov-2006