Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The world's tiniest first responders

21.06.2018

'Walking molecules" haul away damaged DNA to the cell's emergency room

The cell has its own paramedic team and emergency room to aid and repair damaged DNA, a new USC Dornsife study reveals.


An artistic rendering of the mechanism responsible for relocalization of heterochromatic repair sites during homologous recombination. A nuclear myosin walks along a dynamic nuclear actin filament, carrying broken DNA for repair.

Credit: Yekaterina Kadyshevskaya, USC

The findings are timely, as scientists are delving into the potential of genome editing with the DNA-cutting enzyme, CRISPR-Cas9, to treat diseases or to advance scientific knowledge about humans, plants, animals and other organisms, said Irene Chiolo, Gabilan Assistant Professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

Genome editing has arrived before scientists have thoroughly studied the significance and impact of DNA damage and repair on aging and disease, such as cancer. Chiolo's work has been revealing more about those processes.

For the study published today in Nature, Chiolo and her team of researchers at USC Dornsife, using fluorescent markers, tracked what happened when DNA was damaged in fruit fly cells and mouse cells. They saw how the cell launches an emergency response to repair broken DNA strands from a type of tightly-packed DNA, heterochromatin.

"Heterochromatin is also referred to as the 'dark matter of the genome,' because so little is known about it," said Chiolo. "But DNA damage in heterochromatin is likely a major driving force for cancer formation."

Don't call it junk

Repeated DNA sequences have had a bad nickname, "junk DNA," for about 20 years. Scientists decoding the genome called it junk because they were initially focused on understanding the functions of individual genes.

Since then, studies have shown that repeated DNA sequences are in fact essential for many nuclear activities, but their defective repair is also linked to aging and disease.

"Heterochromatin is mostly composed of repeated DNA sequences," Chiolo said. "The low gene content is part of the reason why these sequences are less characterized."

In fact, mutations that compromise heterochromatin repair result in massive chromosome rearrangements affecting the entire genome.

First responders take a walk

The scientists found that after the DNA strands are broken, the cell prompts a series of threads-- nuclear actin filaments-- to assemble and create a temporary highway to the edge of the nucleus. Then come the paramedics -- proteins known as myosins.

"Myosins are conveyed as a walking molecule because they have two legs. One is attached and the other moves. It's like a molecular machine that walks along the filaments."

The myosins pick up the injured DNA, walk along the filament road and then reach the emergency room, a pore at the periphery of the nucleus.

"We knew, based on our prior study, that there was an emergency room -- the nuclear pore where the cell fixes its broken DNA strands. Now, we have discovered how the damaged DNA travels there" Chiolo said. "What we think is happening here is that the damage triggers a defense mechanism that quickly builds the road, the actin filament, while also turning on an ambulance, the myosin."

The researchers plan further studies examining the repair of DNA in heterochromatin.

"I'm excited to see how the molecular mechanisms we uncovered work in humans, as well as in plants that have much larger heterochromatin. It will be fascinating to see how such a complex repair mechanism functions and evolves over time and what aspects of the mechanisms may be adapted for other functions," said Christopher Caridi, a co-lead author for the study and a postdoctoral researcher in Chiolo's lab at USC Dornsife.

###

Other study co-authors were Carla D'Agostino (co-lead author), as well as Taehyun Ryu, Grzegorz Zapotoczny, Laetitia Delabaere, Xiao Li, Varandt Y. Khodaverdian, Emily Lin and Alesandra Rau, all at USC Dornsife's Department of Molecular and Computational Biology. Co-author Nuno Amaral, formerly of the department, is at the Karolinska Institute in Sweden.

The study was supported by a grant from the USC Gold Family and Research Enhancement Fellowships to Taehyun Ryu, as well as a NIH R01 (GM117376), a Mallinckrodt Foundation Award, and a National Science Foundation Career grant (1751197) to Chiolo.

Media Contact

Emily F Gersema
gersema@usc.edu
213-361-6730

 @USC

http://www.usc.edu 

Emily F Gersema | EurekAlert!
Further information:
http://dx.doi.org/10.1038/s41586-018-0242-8

Further reports about: DNA DNA damage DNA sequences DNA strands heterochromatin myosins

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>