PUBLIC RELEASE DATE:

8-Jan-2014

Contact: Lisa Greiner Lisa.Greiner@nyumc.org 212-404-3532 NYU Langone Medical Center / New York University School of Medicine

Our health depends in large part upon the ability of specialized enzymes to find and repair the constant barrage of DNA damage brought on by ultraviolet light radiation and other sources. In a new study NYU School of Medicine researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease.

The study, led by Evgeny Nudler, PhD, a Howard Hughes Medical Investigator and the Julie Wilson Anderson Professor of Biochemistry at NYU Langone Medical Center, is being published online in the January 8 issue of Nature.

Scientists have long known that RNA polymerase slides along the telltale tracks of double-stranded DNA and uses that template to create a growing chain of RNA molecules. This RNA chain, in turn, contains all of the information needed to construct cellular proteins. The enzyme, however, can stall as it patrols the tracks and encounters significant DNA damage. Even worse, it can become lodged over the damaged site, preventing any repair specialists from reaching it.

In the new study, the NYU School of Medicine researchers reveal how another enzyme called UvrD helicase acts like a train engine to pull the RNA polymerase backwards and expose the broken DNA so a repair crew can get to work.

The finding has major implications for a patching mechanism that is widely shared by organisms ranging from bacteria to humans, says Dr. Nudler. "Better repair means fewer mutations, which also means slower aging, less cancer and many other pathologies," he says.

Although the research, conducted in Escherichia coli bacteria, focused on one type of DNA repair, Dr. Nudler says the evidence suggests that other cellular repair pathways might use the same mechanism to recognize and then resolve the damage. Failure to do so can lead to profound consequences: inherited defects in the gene that encodes the human analog of UvrD, a protein known as XPB, have been linked to a range of devastating disorders.

In a condition known as xeroderma pigmentosum, for example, the faulty DNA repair system cannot fix damage caused by ultraviolet radiation. Consequently, any exposure to sunlight can cause serious skin and eye damage and greatly elevate the risk of skin cancer Similarly, children born with Cockayne syndrome age prematurely and are often short in stature due to inadequate DNA repair. Those with a third related condition called trichothiodystrophy have brittle hair, recurrent infections and delayed development.

Read the original here:

Molecular engines star in new model of DNA repair