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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>