PHILADELPHIA - Researchers at the University of Pennsylvania School of Medicine are delving into the details of the complex structure at the ends of chromosomes. Recent work, e-published in Nature Structural & Molecular Biology last month, describes how these structures, called telomeres, can be protected by caps made up of specialized proteins and stacks of DNA called G-quadruplexes, or "G4 DNA." Telomere caps are like a knot at the end of each chromosome "string," with the knot's role preventing the string from unraveling.
"Although G4 DNA has been studied in test tubes for years, we did not know whether it could contribute to telomere protection in actual cells until we performed our studies in yeast cells," stated F. Brad Johnson, MD, PhD, associate professor of Pathology and Laboratory Medicine.
The composition of the particular G4-molecular "knot" studied is complex and unusual, involving a DNA sequence with guanine building blocks that loop back and forth on top of each other to form a four-stranded stack, which is different from the two-stranded arrangement of typical DNA molecules. The stack protects the chromosome from unraveling by specialized enzymes.
The length of telomeres is associated with age. Shortened telomeres are observed in aging cells and in some rare syndromes. There is mounting evidence that loss of telomere capping may contribute to some diseases that become more common with natural aging. An example of extreme aging associated with telomere defects is Werner syndrome, a rare genetic disease in which individuals develop normally until puberty. After this they age rapidly, so that by age 40 or so they often appear several decades older.
The protein missing in people with Werner syndrome but present in healthy people, is a helicase, an enzyme that unzips DNA. A slightly different G4-unwinding helicase is missing in people with a related disease, called Bloom syndrome, which is characterize
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine