Breakthrough technique unveils secrets of “backtracking” in gene regulation

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Summary: A new technique has been developed that can determine the frequency and location of a molecular event called "backtracking" in the genome of any species. This event is believed to be a form of gene regulation that influences many human genes involved in basic life processes. The technique was developed by researchers at NYU Grossman School of Medicine and can provide insights into the role of backtracking in gene expression and potential implications for cell division and development.

A technique can determine for the first time how frequently, and exactly where, a molecular event called “backtracking” occurs throughout the genetic material (genome) of any species, a new study shows.

Published online February 9 in Molecular Cell, the study results support the theory that backtracking represents a widespread form of gene regulation, which influences thousands of human genes, including many involved in basic life processes like cell division and development in the womb.

Led by researchers from NYU Grossman School of Medicine, the work revolves around genes, the stretches of DNA molecular “letters” arranged in a certain order (sequence) to encode the blueprints for most organisms. In both humans and bacteria, the first step in a gene’s expression, transcription, proceeds as a protein “machine” called RNA polymerase II ticks down the DNA chain, reading genetic instructions in one direction.

In 1997, Evgeny Nudler, PhD and colleagues published a paper that showed RNA polymerase can sometimes slip backward along the chain it is reading, a phenomenon they named “backtracking.” Studies since then have shown that backtracking occasionally takes place in living cells soon after RNA polymerase begins RNA synthesis or when it encounters damaged DNA to make room for incoming repair enzymes. Subsequent work suggested that the backsliding and repair machinery had to work quickly and dissipate, or it might collide with DNA polymerase to cause cell-death-inducing breaks in DNA chains.

Now a new study led by Nudler’s team at NYU Langone Health reveals that their new technique, Long Range

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