Why damaged DNA gets a case of the bends

August 22, 2004

PHILADELPHIA -- Our knees may become stiff when injured, but banged up DNA becomes flexible, suggests the most detailed computer model of damaged DNA to date. Further, this flexibility explains how the body's enzymes recognize and fix damaged DNA.

"There's a lot of discussion in the literature about how damaged DNA is recognized by the repair enzymes," said Maciej Haranczyk, a staff scientist at the Department of Energy's Pacific Northwest National Laboratory in Richland, Wash. "The current picture is that some enzymes bend damaged DNA in order to repair altered fragments. But no one knew why damaged DNA was more susceptible to bending."

Haranczyk and colleagues' simulation, reported Sunday at the American Chemical Society national meeting, offers an explanation. First, they programmed a chemical change to an intact DNA fragment. As with real DNA, the simulated molecule's backbone became distorted and its base pairs displaced. The structural change corresponded with a change in the molecule's shape, in its energy and how electric charges are distributed throughout the molecule.

"All these features are significant in enzymatic recognition of the damaged site," Haranczyk said. "In our model, damage triggers a reorganization of the sugar-phosphate in the DNA's backbone such that the DNA becomes thinner. In damaged DNA, negatively charged phosphate groups migrate along the axis of the DNA, and that allows the molecule to bend easily. We believe it is this difference in the damaged and intact DNA that the enzymes recognize."

Haranczyk said this was the first quantum chemistry simulation to survey such a large biological system--in this case, a DNA fragment made up of 350 atoms. "With a system so big, one can't do this kind of work without a supercomputer. Fortunately, we had access to one of the world's 10 most powerful computers," housed at the W.R. Wiley Environmental Molecular Sciences Laboratory on the PNNL campus.

PNNL ( www.pnl.gov ) is a DOE Office of Science laboratory that solves complex problems in energy, national security, the environment and life sciences by advancing the understanding of physics, chemistry, biology and computation. PNNL employs 3,800, has a $600 million annual budget, and has been managed by Ohio-based Battelle since the lab's inception in 1965.
-end-


DOE/Pacific Northwest National Laboratory

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.