Nav: Home

New study reveals the structure of DNA helicase at the replication fork

January 16, 2017

GRAND RAPIDS, Mich. (Jan. 16, 2017)--Scientists at Van Andel Research Institute and Rockefeller University have successfully described a crucial structure involved in DNA replication, placing another piece in the puzzle of how life propagates.

The latest study from long-time collaborators Huilin Li, Ph.D., and Michael O'Donnell, Ph.D., published today in the Proceedings of the National Academy of Sciences, elucidates the interaction between DNA and the eukaryotic enzyme CMG helicase, which opens the DNA double helix like the slider of a zipper and prepares the genetic code for copying.

"Since discovery of the DNA double helix more than 50 years ago, helicase's activity in preparing DNA for replication has been poorly understood," says Li, professor at Van Andel Research Institute. "However, recent advances in microscopy and study design allow us to create accurate images of these enzymes and observe their interactions with DNA for the first time."

More than 40 diseases, including many cancers, anemias and ataxias, in addition to several rare and orphan disorders, trace their origins at least partially to inaccuracy or failures in DNA replication. Results of this study offer a schematic for a core driver behind DNA replication, which Li and O'Donnell hope will eventually help the development of new treatments for these diseases.

"Biologists have learned a great deal about the molecular structure and functions of the enzymes and proteins related to DNA replication," says O'Donnell, professor at Rockefeller University and Howard Hughes Medical Institute investigator. "However, we still have much to discover, and this understanding of helicase activity brings us another step closer."

Findings from the new study reverse a long-held assumption about the orientation of helicase around DNA. Images taken during DNA unwinding demonstrate that helicase's N-tier ring leads the C-tier motor ring and makes first contact with double-stranded DNA. Such orientation is opposite from the currently accepted polarity and has important implications in understanding the mechanism of replication.

Helicase activity has long been recognized as a critical part of DNA replication, itself a fundamental process in the propagation of life. With the publication of this study, scientists have a more complete picture of how most advanced life on Earth proliferates.

This study involved evaluation of CMG helicase purified from the baker's yeast Saccharomyces cerevisiae, an organism commonly used to model higher eukaryotes, including humans.

The structure of the helicase on DNA was derived at Rockefeller University's cryo-electron microscopy (cryo-EM) core facility, leveraging a groundbreaking imaging technology that has revolutionized scientists' ability to visualize and understand the role of fundamental biological processes.

With VARI's recent installation of its own world-class Cryo-EM Core, including the powerful Titan Krios, Li expects the pace of discovery and understanding of these basic biological processes will accelerate in Grand Rapids.
Study authors include Roxana Georgescu, Dan Zhang, Olga Yurieva, and Michael O'Donnell, all of Rockefeller University and Howard Hughes Medical Institute; Lin Bai and Huilin Li, of Van Andel Research Institute; Zuanning Yuan and Ruda de Luna Almeida Santos of Stony Brook University; and Jingchuan Sun, of University of Pennsylvania. Yuan and de Luna Almeida Santos also are affiliated with VARI.

Funding for the study came from Van Andel Research Institute, Howard Hughes Medical Institute and the National Institute of General Medical Sciences of the National Institutes of Health under Award Number GM111742. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About Van Andel Institute

Van Andel Institute (VAI) is an independent nonprofit biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 360 scientists, educators and staff. Van Andel Research Institute (VARI), VAI's research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson's and other diseases and translating those findings into effective therapies. The Institute's scientists work in onsite laboratories and participate in collaborative partnerships that span the globe.

About The Rockefeller University

The Rockefeller University is the world's leading biomedical research university and is dedicated to conducting innovative, high-quality research to improve the understanding of life for the benefit of humanity. Our 79 laboratories conduct research in neuroscience, immunology, biochemistry, genomics, and many other areas, and a community of 1,800 faculty, students, postdocs, technicians, clinicians, and administrative personnel work on our 14-acre Manhattan campus. Our unique approach to science has led to some of the world's most revolutionary and transformative contributions to biology and medicine. During Rockefeller's 115-year history, 24 of our scientists have won Nobel Prizes, 21 have won Albert Lasker Medical Research Awards, and 20 have garnered the National Medal of Science, the highest science award given by the United States.

Van Andel Research Institute

Related Dna Articles:

Penn State DNA ladders: Inexpensive molecular rulers for DNA research
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
It is easier for a DNA knot...
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
How do metals interact with DNA?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
Electrons use DNA like a wire for signaling DNA replication
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
Switched-on DNA
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Researchers are first to see DNA 'blink'
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
Finding our way around DNA
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
A 'strand' of DNA as never before
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
Doubling down on DNA
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
'Poring over' DNA
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.

Related Dna Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...