New Imaging Technique Provides Insights on Telomere Structure

A new microscopy technique enables direct visualization of DNA wrapping outside and around histone proteins, such as in telomeres.

Developed by researchers at North Carolina State University (NCSU; Raleigh, USA), the new imaging technique, known as dual-resonance-frequency-enhanced electrostatic force microscopy (DREEM), utilizes the fact that DNA is negatively charged along its backbone. By applying both direct and alternating current biases between the atomic force microscopy (AFM) probe and the sample surface, the technique can detect very weak electrostatic interaction differences when it scans over protein, as compared to DNA regions.

By using DREEM, the researchers were able to see the DNA's path through the T-loop formation created by telomeric repeat-binding factor 2 (TRF2), a key protein in telomere complex structural integrity. The researchers were thus able to envisage how TRF2 compacts DNA, concluding that there may be two orders of DNA compaction within the telomere. First, DNA wraps around a TRF2 protein in the interior of the complex; then, multiple TRF2 molecules come together and create DNA loops that stick out from the TRF2 proteins. The study was published on February 9, 2016, in Nature Scientific Reports.

“We think that this protruding loop provides the entering site for the telomere overhangs to tuck in to form the T-loop structure. This process ultimately helps to maintain the protective structure that prevents fusion of chromosomes or the slow erosion of telomere DNA,” said lead author physicist Hong Wang, PhD. “Revealing DNA paths in TRF2 complexes provides new mechanistic insights into structure-function relationships underlying telomere maintenance pathways.”

Telomeres are essentially caps on the ends of linear DNA chromosomes. In healthy cells, telomeres protect the chromosome by tucking away any overhanging ends of DNA strands to form a lasso-like structure known as a T-loop. Loss of telomere function can activate a DNA damage response, leading to cell senescence, nucleolytic degradation of the natural chromosome ends, or end-to-end fusions.

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