Scientists discover first 'DNA ambulance'

July 24, 2015, University of Toronto

U of T researchers have discovered how severely damaged DNA is transported within a cell and how it is repaired.

It's a discovery that could unlock secrets into how cancer operates—a disease that two in five Canadians will develop in their lifetime.

"Scientists knew that severely injured DNA was taken to specialized 'hospitals' in the cell to be repaired, but the big mystery was how it got there," said Karim Mekhail, a Professor in the Faculty of Medicine's Department of Laboratory Medicine and Pathobiology. "We've now discovered the DNA 'ambulance' and the road it takes."

Mekhail discovered this DNA ambulance, which is a motor protein complex, by using . His research was recently published in Nature Communications.

Mekhail's team also found that the DNA hospital, also known as the , repairs damaged DNA inaccurately.

This inaccurate fix is important because DNA contains the instructions for all our genetic information. While the repaired DNA can still replicate, it has irregular cell instructions—a scenario that could cause cancer.

"This process allows cells to survive an injury, but at a great cost," said Mekhail. "The cell has a compromised genome, but it's stable and can be replicated, and that's usually a recipe for disaster."

Co-author Daniel Durocher, Senior Investigator at Mount Sinai's Lunenfeld-Tanenbaum Research Institute, helped the team track the damaged DNA in living cells by using advanced microscopy. The tracking showed that this DNA ambulance is necessary for damaged DNA to efficiently change location within the nucleus.

"Cancer often occurs when our chromosomes break and are misrepaired," said Durocher. "This work teaches us that the location of the break within the cell's nucleus has a big impact on the efficiency of repair."

The implications of the research could extend to a large number of developmental and disease settings.

"The processes we're studying are fundamental to the basic survival of a cell," said graduate student and first author Daniel Chung. "Almost every aspect of disease can be linked to problems with DNA."

Now Mekhail's team is searching for more DNA ambulances and roads while conducting a study to see what role they might play in causing cancer. "We expect that this may allow us to identify targets for a new class of anti-cancer drugs."

"Scientists have been searching for this DNA for a long time and now we suspect there may be more than one," said Mekhail. "It's exciting because it's a whole new area of research."

Explore further: A novel DNA damage alarm

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JVK
1 / 5 (1) Jul 25, 2015
I do not get the impression that DNA repair can be linked from yeasts to humans via what is currently known about biophysically constrained protein folding chemistry that is nutrient-dependent and RNA-mediated in the context of gene duplication and cell type differentiation.

Fixation of RNA-mediated amino acid substitutions stabilizes the organized genomes of all genera via the physiology of their reproduction. Why is this report ignoring the difference between repair mechanisms and virus-driven pathology?

Is it not clear that the physiology of reproduction in yeasts is nutrient-dependent and pheromone-controlled, or would information on RNA-mediated DNA repair link nutrient-dependent and pheromone-controlled cell type differentiation from yeasts to humans via the biophysically constrained chemistry of RNA-mediated protein folding in all living genera?
Vietvet
3 / 5 (2) Jul 25, 2015
I do not get

There's a lot jvk doesn't get, especially evolution.
JVK
1 / 5 (1) Jul 26, 2015
Eugene Koonin recently realized that the "Modern Synthesis" does not include anything currently known to serious scientists about virus-induced entropic elasticity.

http://www.huffin...216.html

"The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis..."

Whatever other evolutionary theorists think they know about evolution can be placed in that perspective. Simply put, theorists know nothing about how evolution occurs. When pressed for an intelligent answer, they claim it "just happens."

"Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed "the blind watchmaker." To some extent, it just happens." -- Carl Zimmer (2013)
anonymous_9001
5 / 5 (2) Jul 26, 2015
1. You better understand all this math and engineering if you're going to adopt the term "entropic elasticity" into your model:

http://link.sprin...7#page-1
http://repository...ons/371/

Something tells me you don't.

2. As with Noble and the rest you cite, Koonin isn't saying the Modern Synthesis is outright false. He's just saying it's incomplete. Nobody denies that.

3. He talks about the LUCA in that article, something you detest.
JVK
1 / 5 (1) Jul 26, 2015
Hi Andrew Jones (aka anonynmous_9001)

See also: http://medicalxpr...ics.html

Koonin addressed the pseudosceintific nonsense about LUCA in 2005. See "A universal trend of amino acid gain and loss in protein evolution."

"We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms."

The light-induced de novo creation of amino acids appears to link the sun's biological energy from RNA-mediated gene duplication and RNA-mediated amino acid substitutions to all of earth's biomass. What are you claiming about LUCA and/or the role of mutations?
anonymous_9001
5 / 5 (2) Jul 26, 2015
As usual, you completely miss the point of that excerpt. He's not denying the existence of a LUCA, he's saying that the AA composition was established in the LUCA and then passed down rather than happening independently in the 15 taxa. Learn to read, for crying out loud.
JVK
1 / 5 (1) Jul 26, 2015
See also: journalist RF Service http://www.scienc...98.short
and
http://www.scienc...72.short

The importance of nutrient-dependent RNA-mediated DNA repair can be linked from the de novo creation of amino acids to fixation of substitutions in all organized genomes via the physiology of reproduction.

Serious scientists realize that facts links viruses to pathology and nutrient-dependent microRNAs to healthy longevity via DNA repair. That's why they are "Combating Evolution to Fight Disease" http://www.scienc...88.short

The combatants include information about biologically-based cause and effect that links nutritional epigenetics to pharmacogenomics and personalized medicine. Koonin states: "[T]he entire ideology of personalized medicine should be taken with many grains of salt."

What else could he say after ignoring the role of virus-perturbed nutrient-dependent ecological adaptations?
JVK
1 / 5 (1) Jul 26, 2015
Re: "...the AA composition was established in the LUCA..."

If you insist on adding more of your pseudoscientific nonsense, there will be no informed debate. You start with the automagical appearance of amino acids and link them to changes in morphology and behavior via mutations that perturb protein folding. Why not simply admit that you know nothing about physics, chemistry, or the conserved molecular mechanisms of RNA-mediated cell type differentiation that I have included in a series of published reviews during the past two decades?

If Koonin can admit that the role of viruses has been ignored, others will be forced to do so. The biologically uninformed will be removed from any debate. The first to be removed should have been you -- more than a year ago, when you published Criticisms of the nutrient-dependent pheromone-controlled evolutionary model http://www.ncbi.n...4049134/

You failed to provide an alternative model for debate.

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