Nav: Home

Squeezing life from DNA's double helix

December 12, 2016

For years, scientists have puzzled over what prompts the intertwined double-helix DNA to open its two strands and then start replication. Knowing this could be the key to understanding how organisms - from healthy cells to cancerous tumors - replicate and multiply for their survival.

A group of USC scientists believe they have solved the mystery. Replication is prompted by a ring of proteins that bond with the DNA at a special location known as "origin DNA." The ring tightens around the strands and melts them to open up the DNA, initiating replication.

This all takes place at a nano level that is impossible to see with the naked eye. A strand of DNA is only about one nanometer in size - not even close to the width of a human hair which is roughly equivalent to 100,000 DNA strands.

The researchers made their discovery by studying a cancerous virus, SV40. The virus hijacked the DNA replication process with a ring of proteins, called a "helicase" that mimicked the rings of proteins that prompt genetic replication in healthy cells.

The findings were published on Dec. 6 in the journal eLife.

"Understanding the mechanisms of origin DNA opening or melting allows us to learn this fundamental process of genetic duplication," said corresponding author Xiaojiang Chen, a professor of biological sciences and chemistry in the USC Dornsife College of Letters, Arts and Sciences and director of the college's Center of Excellence in NanoBiophysics. "The knowledge we have gained may be applicable for future intervention of this process to block the replication of viral pathogens and cancer cells."

Xerox copies

When the origin DNA melts, the double helix divides into separate strands, Chen explained. Those DNA strands then become the template for faithful duplication of other strands - a Xerox copy of their parental DNA. As soon as replication is complete, one double helix DNA now becomes two exact copies of the same double helix.

"DNA replication is critical for heredity and survival," said Chen, who also is affiliated with the Norris Comprehensive Cancer Center at the Keck School of Medicine at USC. "The origin DNA's opening is an essential step for DNA replication in our cells and for some tumor viral pathogens to replicate and spread."

Why is origin DNA so special? Regular DNA sequences contain the A, T, G and C nucleotides, more or less in equal ratio. But origin DNA sequences contain more A and T nucleotides than usual.

To prompt replication, the scientists used a helicase from a "Large Tumor Antigen" or Large T. The antigen comes from a virus, SV40, linked to human cancers such as brain and bone cancers, mesothelioma and lymphoma. The six proteins from Large T comprise a "helicase" that mimics the structure of the healthy cells' helicases.

The scientists obtained a 3-D view of the atomic structure of the helicase using X-ray crystallography, a technique for examining nano-biomolecules and their structures at the atomic level that has been refined over centuries. Chen said the images revealed that the proteins which surrounded the DNA had attached to it, then tightened like a vice until the bonds between the two strands of the double helix broke - or melted - the origin DNA.

Although the scientists used a cancerous virus to study replication, healthy cells replicate in a similar way, Chen said.
Other co-authors were Dahai Gai, also of USC Dornsife, Damian Wang of the Keck School of Medicine at USC, and Shu-Xing Li of USC Dornsife's Center for Excellence in NanoBiophysics.

The study was funded by an NIH grant, A1055926.

University of Southern California

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

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...