Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Reveal a New Mechanism of Genomic Instability

22.08.2011
Using E. coli Cells Researchers Show How Collisions Between Major Gene Expression Lead to Chromosomal Breaks

Study May Explain Chromosomal Fragility Associated with Certain Human Diseases

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.

Researchers demonstrated that the cooperation between translating ribosomes and RNA polymerase is central in the maintenance of genomic stability because it prevents backtracking.

The implication of these findings is significant as the ribosome is the primary sensor of cellular metabolism and stress. It has been well established that stress-induced mutagenesis is activated in response to adverse conditions, such as starvation or antibiotics. The development of mutations depends on error-prone DSB repair, which accelerates adaptation to environmental changes, such as acquisition of resistance to antibiotics. In this respect, the backtracking-based mechanism of DSB may account for stress-driven evolution in bacteria.

“Because the organization of replisomes and RNA polymerase is preserved in evolution, the phenomena of backtracking-driven genome instability for E.coli could occur in other organisms as well. It may potentially explain, for example, some cases of chromosomal fragility associated with certain human diseases” said Dr. Nudler.

About NYU Langone Medical Center
NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation’s premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world’s first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousand of physicians and scientists who have helped to shape the course of medical history. The medical center’s tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research.

Christopher Rucas | Newswise Science News
Further information:
http://www.NYULMC.org

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>