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
Christopher Rucas | Newswise Science News
Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering