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 from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.