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NYU Langone researchers reveal a new mechanism of genomic instability
Date:8/18/2011

NEW YORK, August 18, 2011 Researchers at NYU School of Medicine have discovered the cellular mechanisms that normally generate chromosomal breaks in bacteria such as E. coli. The study's findings are published in the August 18 issue of the journal Cell.

"This study provides a new explanation on how bacteria generate mutations and adapt to stressors like antibiotics. The study is quite unusual as it touches on several different fields of molecular biology at the same time: replication, transcription, translation and DNA repair," said Evgeny Nudler, PhD, The Julie Wilson Anderson Professor of Biochemistry, in the Department of Biochemistry at NYU School of Medicine and co-author of the study.

The study examines the collision of three major cellular moving "machines": replisome a protein complex responsible for DNA synthesis, RNA polymerase an enzyme responsible for RNA synthesis, and ribosome a molecular structure responsible for protein synthesis. Collisions between replisome and RNA polymerase occur frequently in cells because the two machineries share the same DNA track, but the speed of the replisome is much faster than that of RNA polymerase. However, the consequences of such collisions remained unknown.

Researchers designed an experimental system to directly monitor co-directional and head-on collisions between the replisome and RNA polymerase in living cells under various conditions of growth.

Researchers found co-directional collisions lead to DNA double strand breaks (DSBs) or mutations. Importantly, however, such DSBs appear only if the replisome collides with backtracked RNA polymerase.

Backtracking, or backward sliding of RNA polymerase along RNA and DNA, is an intrinsic property of all cellular RNA polymerases from bacteria to humans. Multiple anti-backtracking mechanisms that employ various transcription factors exist in bacteria and nucleus-containing cells, including human cells.

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Contact: Christopher Rucas
christopher.rucas@nyumc.org
212-404-3525
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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