Our genome is constantly under attack from things like UV light and toxins, which can damage or even break DNA strands and ultimately lead to cancer and other diseases.
Scientists have known for a long time that when DNA is damaged, a key enzyme sets off a cellular ‘alarm bell’ to alert the cell to start the repair process, but until recently little was known about how the cell detects and responds to this alarm. In a study published today in Nature Structural and Molecular Biology, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have identified a whole family of proteins capable of a direct response to the alarm signal.
Our genome is a huge repository of information guiding the construction and function of all the cells in our bodies. Cells sustain many hits to their DNA every day, which can lead tomutations, so they maintain a fleet of DNA repair machinery that can be rapidly mobilised and sent to damaged sites in an emergency.
Because our DNA is so long and unwieldy, it needs to be packaged up with proteins and organised into a complex structure called chromatin. Scientists have known for 50 years that one component of chromatin, an enzyme known as PARP1, is activated by DNA damage and produces a molecular signal, called PAR, which raises the alarm at the site of the damage. In recent weeks, scientists have for the first time worked out how PAR is rapidly detected by the cell; in their Nature Structural and Molecular Biology paper, the group of Andreas Ladurner and their colleagues at EMBL have identified a whole family of proteins that respond to this signal by binding to it directly.
What these proteins share is a special region called a macrodomain. By using a laser to reproduce DNA damage in the lab, the scientists were able to follow fluorescently-labelled macrodomain proteins in cells and observed that they quickly move to the site of DNA damage. A high-resolution image, obtained by X-ray crystallography, shows how the macrodomain forms a ‘pocket’ fitting the PAR signal exactly.
Among the members of the family the researchers found a protein called histone macroH2A1.1. “This was very surprising. Histones play a major role in assembling chromatin and keeping it together, but they don’t usually have macrodomains,” says Ladurner. “The finding is particularly relevant, because it turns out that cancer cells don’t have macroH2A1.1. The fact that one member of the rapid response team that detects DNA damage is missing could contribute to the disease.”
Because macroH2A1.1 is embedded in chromatin, when it recognises PAR at DNA damage sites, it drags the complex but highly-organised tangle of chromatin with it. As a result, macroH2A1.1 condenses the chromatin environment around the damaged area.
The scientists are now trying to understand why this happens. One plausible explanation could be that by temporarily compacting the DNA, the broken ends of the DNA molecule are kept closer together. This should increase the chances of being able to repair it.
“With these findings we’ve opened up completely new perspectives to a fifty-year-old field of research,” says Ladurner. “We’re very excited of what lies ahead and hope that we’ll soon be much closer in understanding how PARP1 and macrodomains together maintain a healthy genome.”
Anna-Lynn Wegener | EMBL
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Information Technology
05.12.2016 | Earth Sciences