Navigation Links
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.

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.


'/>"/>

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

Related biology news :

1. NYU Langone experts find MRI techniques can detect early osteoarthritis
2. NYU Langone researchers identify a signaling pathway as possible target for cancer treatment
3. NYU Langone Medical Centers tip sheet to the 2011 Alzheimers Association International Conference
4. NYU Langone experts present advances at American Association of Neurological Surgeons Meeting
5. NYU Langone Medical Center receives $5.4 million NYSTEM grant for stem cell research
6. NYU Langone Medical Center awarded NIH grants totaling $1,560,000
7. NYU Langone Medical Center researchers find micro RNA plays a key role in melanoma metastasis
8. Researchers complete first major survey of amphibian fungus in Asia
9. Researchers find new hope for treatment of chronic leukemia
10. Researchers find way to align gold nanorods on a large scale
11. UBC researchers discover key mechanism that regulates shape and growth of plants
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2016)... -- A market that just keeps on growing. Molecular ... in genomics knowledge. Learn all about it in this ... dynamic trends are pushing market growth and company valuations. ... - pathogen evolution - next generation sequencing - emergence ... of the role of genetic material in Disease and ...
(Date:1/20/2016)... , Jan. 20, 2016  Synaptics Incorporated (NASDAQ: ... interface solutions, today announced sampling of S1423, its ... wearables and small screen applications including smartwatches, fitness ... Supporting round and rectangular shapes, as well as ... performance with moisture on screen, while wearing gloves, ...
(Date:1/15/2016)... 15, 2016 Recent publicized breaches in cyber ... new ways to ensure data security and user authentication ... and Android that ties a user,s mobile ... into a hardware authorization token. Customer service agents who ... on their KodeKey enabled device to verify their identity. ...
Breaking Biology News(10 mins):
(Date:2/10/2016)... ... February 10, 2016 , ... Global ... new agreement with Singapore-based Global Stem Cells Network (GSCN) and its affiliate ... Singapore in the latest adipose and bone marrow therapies. , Through the ...
(Date:2/9/2016)... , ... February 09, 2016 , ... With a presidential ... Wharton Health Care Business Conference will bring together over 500 top healthcare leaders for ... industry in transformation. The conference, organized by MBA students of the University of Pennsylvania’s ...
(Date:2/9/2016)... ... February 08, 2016 , ... ... services, announced today the launch of its revamped and improved website. In an ... service solutions, the redesigned website will better communicate how the company designs and ...
(Date:2/9/2016)... ... February 09, 2016 , ... The American Academy ... history, it is offering its 2016 AAT Member Certification Qualification Course for Technicians via ... for the webinar, which will include a detailed review of hardware, software, and camera ...
Breaking Biology Technology: