Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research Resolves a Mystery in DNA Replication Process

26.09.2011
DNA replication is a basic function of living organisms, allowing cells to divide and multiply, all while maintaining the genetic code and proper function of the original cell.

This is accomplished as the double helical (coil-shaped) DNA divides into two strands that are then duplicated. New research from UMDNJ-Robert Wood Johnson Medical School and Cornell University identifies how the ring-shaped helicase enzymes that separate the strands of double helical DNA track forward along the DNA without slipping backward.

Ring-shaped helicases are key players in replicating not only the human genome but those of pathogenic viruses (viruses with the ability to cause disease) such as the human papilloma virus (HPV) that causes cervical cancer. It is hoped that understanding how this class of helicases works will pave the way to new therapeutic treatments for human diseases.

The study, “ATP-induced helicase slippage reveals highly coordinated subunits,” was chosen for advanced online publication in Nature this week, and can be found online at: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10409.html.

To initiate unwinding of DNA, the helicase enzymes rely on the presence of nucleotides (molecules that are basic building blocks of DNA and RNA), generally a nucleotide called adenosine triphosphate or ATP. However, when explicitly examining DNA unwinding with ATP, the research team discovered that the phage T7 helicase unwinds DNA with ATP at a fast rate but it slips repeatedly.

“To our knowledge this is the first direct observation of helicase nucleotide-specific slippage, and our detailed study of this phenomenon reveals a potential mechanism for ensuring successful unwinding and duplication of DNA,” said Smita Patel, PhD, professor of biochemistry at UMDNJ-Robert Wood Johnson Medical School, along with her collaborator Michelle Wang from Cornell University and the Howard Hughes Medical Institute.

However, the researchers found that helicase slippage was stopped when another nucleotide, deoxythymidine triphosphate, or dTTP, was added to ATP, and that mixtures of ATP and dTTP controlled the degree of slippage.

“Through further examination of the DNA unwinding reaction with mixtures of ATP and dTTP, we discovered the mechanism by which the helicase subunits coordinate their activities to ensure efficient strand separation without falling off the DNA,” said Dr. Patel.

The study explains that for a helicase to slip, all six of its subunits must simultaneously lose their grip on the DNA. The presence of dTTP increased the helicases’ ability to bind successfully to DNA, thereby reducing slippage. The team explains that each of the subunits takes a turn in assuming the leading position to pull on the DNA and to move the helicase ring forward. This work reveals that while the leading subunit is pulling on the DNA, the remaining subunits are holding on to the DNA and helping the leading subunit to move forward without falling off the DNA. Holding on to the DNA tightly requires some amount of dTTP, and explains how dTTP prevents helicase slippage. This type of cooperation between the helicase ring subunits makes the helicase effective at unwinding DNA. If the process of DNA unwinding was interrupted by slippage of the helicase, and was left uncorrected, it would stall the replication process causing harm to the normal cell growth.

The research was supported by grants from the National Institutes of Health and the National Science Foundation and Cornell’s Molecular Biophysics Training Grant.

About UMDNJ-ROBERT WOOD JOHNSON MEDICAL SCHOOL

As one of the nation’s leading comprehensive medical schools, UMDNJ-Robert Wood Johnson Medical School is dedicated to the pursuit of excellence in education, research, health care delivery, and the promotion of community health. In cooperation with Robert Wood Johnson University Hospital, the medical school’s principal affiliate, they comprise New Jersey’s premier academic medical center. In addition, Robert Wood Johnson Medical School has 34 other hospital affiliates and ambulatory care sites throughout the region.

As one of the eight schools of the University of Medicine and Dentistry of New Jersey with 2,800 full-time and volunteer faculty, Robert Wood Johnson Medical School encompasses 22 basic science and clinical departments, hosts centers and institutes including The Cancer Institute of New Jersey, the Child Health Institute of New Jersey, the Center for Advanced Biotechnology and Medicine, the Environmental and Occupational Health Sciences Institute, and the Stem Cell Institute of New Jersey. The medical school maintains educational programs at the undergraduate, graduate and postgraduate levels for more than 1,500 students on its campuses in New Brunswick, Piscataway, and Camden, and provides continuing education courses for health care professionals and community education programs. To learn more about UMDNJ-Robert Wood Johnson Medical School, log on to rwjms.umdnj.edu. Find us online at www.Facebook.com/RWJMS and www.twitter.com/UMDNJ_RWJMS.

Jennifer Forbes | Newswise Science News
Further information:
http://www.rwjms.umdnj.edu

More articles from Life Sciences:

nachricht Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>