Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Paths Explored for Curbing Genetic Malfunctions

Published: Tuesday, February 19, 2013
Last Updated: Tuesday, February 19, 2013
Bookmark and Share
Investigators probe mechanisms of RNA synthesis.

One of the most extraordinary properties of living cells is their ability to precisely reproduce themselves through processes that transfer genetic information from one cell to the next. However, there are times when one of the steps of information transfer, transcription, goes awry at the cellular level, potentially producing diseases such as cancer and other health disorders. Unraveling how those processes work and how substandard transcription can be prevented is a major goal of biomedical science. Progress in this area may also lead the way toward development of drugs that target the genetic transcription process in disease-causing microbes.

A research team led by Arkady Mustaev, PhD, of the Public Health Research Institute (PHRI) at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, has published a study posted online by the Journal of Biological Chemistry, that describes an effort by the investigators to understand the underlying mechanisms of high precision (fidelity) of RNA synthesis by RNA polymerase, the major enzyme that promotes the transcription process. They attempted to influence the role of active center tuning (ACT) -- a mechanism they first identified -- in the process of transcription fidelity, which is the accurate copying of genetic information.

ACT is a rearrangement of the RNA polymerase catalytic center from an inactive to a catalytically proficient state. The investigators found that both reactions of NTP polymerization and hydrolytic RNA proofreading are performed by the same active center that includes two magnesium (Mg) ions coordinated by aspartate triad. The active center is normally “turned off” since it is missing one of Mg ions. Correct NTP substrates as well as misincorporated RNA residues can promote ACT by inclusion of the missing Mg ion through establishing recognition contacts in the active center. Incorrect substrates cannot trigger ACT and are rejected. The investigators also demonstrate that transcript cleavage factors Gre build on ACT mechanism by providing the residues for stabilization of catalytic Mg ion and for activation of the attacking water causing 3000-4000-fold reaction enhancement thereby strongly reinforcing proofreading.

The suggested ACT mechanism is fundamentally different from that proposed for DNA replication enzyme, DNA polymerase (DNAP) in which the active centers for DNA synthesis and proofreading are separated and discrimination between deoxy- and ribo-substrate is achieved through strict fitting requirements for the sugar rather than through active center rearrangement. In DNAP active center carboxylates stem from rigid scaffolds, while in multisubunit RNAP they reside in an apparently flexible loop. ACT is accompanied by significant re-shaping of the loop, which would not be possible in DNAP.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More Than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Criminal Justice Alcohol Program Linked to Decreased Mortality
Institute has announced that in the criminal justice alcohol program deaths dropped by 4.2 percent over six years.
Charting Kidney Cancer Metabolism
Changes in cell metabolism are increasingly recognized as an important way tumors develop and progress, yet these changes are hard to measure and interpret. A new tool designed by MSK scientists allows users to identify metabolic changes in kidney cancer tumors that may one day be targets for therapy.
Improving Regenerative Medicine
Lab-created stem cells may lack key characteristics, UCLA research finds.
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH has announced that decipher the genome of the blacklegged tick which could lead to new tick control methods.
"Dark Side" of the Transcriptome
New approach to quantifying gene "read-outs" reveals important variations in protein synthesis and has implications for understanding neurodegenerative diseases.
Individuals' Medical Histories Predicted by their Noncoding Genomes
Researchers have found that analyzing mutations in regions of the genome that control genes can predict medical conditions such as hypertension, narcolepsy and heart problems.
'Molecular Movie' Opens Door to New Cancer Treatments
An international team of scientists led by the University of Liverpool has produced a 'structural movie' revealing the step-by-step creation of an important naturally occurring chemical in the body that plays a role in some cancers.
New Source of Mutations in Cancer
Recently, a new mutation signature found in cancer cells was suspected to have been created by a family of enzymes found in human cells called the APOBEC3 family.
Advancing Synthetic Biology
Living systems rely on a dizzying variety of chemical reactions essential to development and survival. Most of these involve a specialized class of protein molecules — the enzymes.
Madison Researchers Begin Work on Zika Virus
Work will start with basic questions about Zika virus infection.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!