Wielding a palette of chromosome paints, scientists at the Salk Institute for Biological Studies have taken a step closer to understanding the relationship between aging and cancer by visualizing chromosomes of cells from patients with a heritable premature aging disease known as Werner Syndrome.
In a study to be published in this week's online edition of the Proceedings of the National Academy of Sciences researchers led by Jan Karlseder, Ph.D., assistant professor in Salk's Regulatory Biology Laboratory, showed that rebuilding structures called telomeres, which are found at the tips of each chromosome, significantly blocks the type of genetic damage seen in cells of patients with Werner Syndrome.
Patients with Werner Syndrome manifest signs of aging, such as skin wrinkling, baldness, or hair graying, in their teens. Most die in their 40's or 50's due to a predisposition to diseases like cancer. "Cancer is almost always related to chromosomal instability," explains Karlseder. "If telomeres are lost on individual chromosomes, then chromosomes are not protected and can fuse with other nonprotected chromosomes. Then when cells divide, chromosomes randomly break, leading to genome instability."
The current study extended work published in 2004 by Karlseder and first author Laure Crabbe, Ph.D., who was a graduate student in the Karlseder lab at the time. In that work, the team used a technique called FISH-short for fluorescent in situ hybridization-to microscopically visualize both the telomeres and chromosomal DNA from Werner Syndrome patients. They reported that some protective telomeres were actually missing on patients' chromosomes, a finding Karlseder describes as "a fairly catastrophic event for a cell."
For the current study, Salk researchers grew cells from Werner Syndrome patients in tissue culture dishes and, aided by colleagues at the Institute of Human Genetics in Heidelberg, Germany, evaluated DNA damage using a h
Contact: Gina Kirchweger