Navigation Links
NYU Langone researchers reveal a new mechanism of genomic instability

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
NYU Langone Medical Center / New York University School of Medicine

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:
(Date:4/19/2016)... 2016 The new GEZE SecuLogic ... web-based "all-in-one" system solution for all door components. It ... the door interface with integration authorization management system, and ... The minimal dimensions of the access control and the ... installations offer considerable freedom of design with regard to ...
(Date:4/13/2016)... , April 13, 2016  IMPOWER physicians supporting Medicaid ... setting a new clinical standard in telehealth thanks to ... leveraging the higi platform, IMPOWER patients can routinely track ... and body mass index, and, when they opt in, ... convenient visit to a local retail location at no ...
(Date:3/23/2016)... , March 23, 2016 ... erhöhter Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender ... das Unternehmen mit SpeechPro zusammenarbeitet, um erstmals ... Finanzdienstleistungsbranche, wird die Möglichkeit angeboten, im Rahmen ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016   Boston Biomedical , ... compounds designed to target cancer stemness pathways, announced ... granted Orphan Drug Designation from the U.S. Food ... gastric cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin ... to inhibit cancer stemness pathways by targeting STAT3, ...
(Date:6/23/2016)... SILVER SPRING, Md. , June 23, 2016 ... evidence collected from the crime scene to track the criminal ... sick, and the U.S. Food and Drug Administration (FDA) uses ... Sound far-fetched? It,s not. ... whole genome sequencing to support investigations of foodborne illnesses. Put ...
(Date:6/23/2016)... ... 2016 , ... Charm Sciences, Inc. is pleased to announce ... Research Institute approval 061601. , “This is another AOAC-RI approval of the Peel ... President of Regulatory and Industrial Affairs. “The Peel Plate methods perform comparably to ...
(Date:6/23/2016)... June, 23, 2016  The Biodesign Challenge (BDC), a ... ways to harness living systems and biotechnology, announced its ... in New York City . ... students, showcased projects at MoMA,s Celeste Bartos Theater during ... , MoMA,s senior curator of architecture and design, and ...
Breaking Biology Technology: