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
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences