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.

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