Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Proteomics identifies DNA repair toolbox

04.05.2015

Various repair mechanisms help our cells to revert damage to their DNA. If they fail, mutations accumulate in the genome that can lead to devastating diseases. DNA repair defects underlie predisposition to certain cancers and promote the transformation process in other spontaneous cancers.

DNA repair requires many factors, but so far there have not been comprehensive analyses of the intricate pathways involved. Using novel and highly sensitive proteomic technologies, scientists of the Max Planck Institute (MPI) of Biochemistry now report in the journal Science the first global analysis of the protein recruitment dynamics underlying a critical DNA repair pathway.


Identification of DNA repair proteins by mass spectrometry

Markus Raeschle / MPI of Biochemistry

Their results shed light on the repair mechanism and identified new proteins and drug targets that could be important in maintaining genomic stability and preventing cancer.

During each cell division, more than 3.3 billion base pairs of genomic DNA have to be duplicated and segregated accurately to daughter cells. But what happens when the DNA template is damaged in such a way that the replication machinery gets stuck?

To answer this question, scientists in the team of Matthias Mann at the MPI of Biochemistry in Martinsried near Munich, with colleagues in Copenhagen and at Harvard, have analyzed how the protein composition of the DNA replication machinery changes upon encountering damaged DNA.

To monitor such changes, they isolated DNA at several time points during the replication and repair process, and quantified the bound proteins using mass spectrometry based proteomics. In contrast to the conventional approach of quantifying a few selected proteins, proteomic analysis allows the simultaneous quantification of thousands of proteins from a biological sample.

Using this unbiased approach, they found that as the replication machinery collides with lesions in the DNA more than 90 proteins are recruited to help repair the damaged DNA. These include many known DNA repair factors, as well as new proteins of previously unknown function. Together with the team of Professor Mailand at the Center for Protein Research in Copenhagen, Denmark, they are now analyzing whether and how these proteins promote the repair process.

“Many of these recruited proteins are essential for the faithful propagation of genomic information to daughter cells,” explains Markus Räschle, first author of the study. “Because defects in DNA repair pathways are commonly observed in genetically inherited cancer syndromes, such as familially inherited breast cancer, it is possible that mutations in the new factors may contribute to genetic predisposition to cancers.”

DNA modifying agents are among the most frequently used class of chemotherapeutics. They work particularly well if the cancer cells they attack already have defects in the corresponding DNA repair pathways, as it frequently occurs in breast cancer and other tumors.

Adaptation of proteomics for clinical diagnostics may open completely new possibilities. “Acquiring proteomic profiles directly from the tumor tissue may help oncologists to rapidly find the optimal class and dose of drugs,” says Matthias Mann, director at the Max Planck Institute of Biochemistry. “Our hope is that this approach may lead to more effective therapies with fewer side effects.”

Original publication:
M. Räschle, G. Smeenk, R.K. Hansen, T. Temu, Y. Oka, M.Y. Hein, N. Nagaraj, D.T. Long, J.C. Walter, K. Hofmann, Z. Storchova, J. Cox, S. Bekker-Jensen, N. Mailand, M. Mann: Proteomics reveals dynamic assembly of repair complexes during bypass of DNA crosslinks. Science, May 1, 2015
DOI: 10.1126/science.1253671

Weitere Informationen:

http://www.biochem.mpg.de/5003150/20150504_mann_dnareparatur - detailed press release
http://www.biochem.mpg.de/news/ueber_das_institut/forschungsbereiche/zellbiologi... - more texts about Matthias Mann's research
http://www.biochem.mpg.de/mann - website of the research department "Proteomics and Signal Transduction" (Matthias Mann)

Anja Konschak | Max-Planck-Institut für Biochemie

More articles from Life Sciences:

nachricht Virus multiplication in 3D
13.12.2019 | Julius-Maximilians-Universität Würzburg

nachricht New technique to determine protein structures may solve biomedical puzzles
12.12.2019 | Dana-Farber Cancer Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Cheers! Maxwell's electromagnetism extended to smaller scales

More than one hundred and fifty years have passed since the publication of James Clerk Maxwell's "A Dynamical Theory of the Electromagnetic Field" (1865). What would our lives be without this publication?

It is difficult to imagine, as this treatise revolutionized our fundamental understanding of electric fields, magnetic fields, and light. The twenty original...

Im Focus: Highly charged ion paves the way towards new physics

In a joint experimental and theoretical work performed at the Heidelberg Max Planck Institute for Nuclear Physics, an international team of physicists detected for the first time an orbital crossing in the highly charged ion Pr⁹⁺. Optical spectra were recorded employing an electron beam ion trap and analysed with the aid of atomic structure calculations. A proposed nHz-wide transition has been identified and its energy was determined with high precision. Theory predicts a very high sensitivity to new physics and extremely low susceptibility to external perturbations for this “clock line” making it a unique candidate for proposed precision studies.

Laser spectroscopy of neutral atoms and singly charged ions has reached astonishing precision by merit of a chain of technological advances during the past...

Im Focus: Ultrafast stimulated emission microscopy of single nanocrystals in Science

The ability to investigate the dynamics of single particle at the nano-scale and femtosecond level remained an unfathomed dream for years. It was not until the dawn of the 21st century that nanotechnology and femtoscience gradually merged together and the first ultrafast microscopy of individual quantum dots (QDs) and molecules was accomplished.

Ultrafast microscopy studies entirely rely on detecting nanoparticles or single molecules with luminescence techniques, which require efficient emitters to...

Im Focus: How to induce magnetism in graphene

Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.

Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...

Im Focus: Electronic map reveals 'rules of the road' in superconductor

Band structure map exposes iron selenide's enigmatic electronic signature

Using a clever technique that causes unruly crystals of iron selenide to snap into alignment, Rice University physicists have drawn a detailed map that reveals...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Fraunhofer IPT and Ericsson launch 5G-Industry Campus Europe, Europe’s largest Industrial 5G Research Network

13.12.2019 | Information Technology

Light, strong, and tough: Researchers at the University of Bayreuth discover unique polymer fibres

13.12.2019 | Materials Sciences

Weizmann physicists image electrons flowing like water

12.12.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>