Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sentinels of the Genome

16.03.2018

A comprehensive resource reveals dynamics of 70 DNA repair proteins - a powerful platform for basic research and anticancer drug evaluation.

Throughout life, DNA is constantly being damaged by environmental and intrinsic factors and must be promptly repaired to prevent mutations, genomic instability, and cancer. Different types of damages are repaired by numerous proteins organized into damage-specific pathways.


Recruitment of two proteins to the sites of DNA damage generated by laser micro-irradiation.

Stoynov/ IMB-BAS

The proteins from different pathways must be spatially and temporally coordinated in order to efficiently repair complex DNA damages. How this is achieved by the cell, is still poorly understood, due to the complexity and rapid dynamics of the process.

This question is particularly important since many anticancer drugs either damage DNA or target DNA repair proteins. A systematic study of the impact of such drugs on the overall coordination of the repair process could deliver new insights into their mechanisms of action, prompt new applications or suggest possible side effects.

An international team of researchers from the Institute of Molecular Biology at the Bulgarian Academy of Sciences (IMB-BAS), Sofia University, the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), the Biotechnology Center (BIOTEC) and the Medical Faculty, both at the TU Dresden, and the Department of Mathematics of University of Pennsylvania built a high resolution, quantitative model of the dynamics of arrival and departure of 70 key DNA repair proteins at sites of complex DNA damage.

The researchers present their findings in the current issue of Molecular Cell. Combining the proteins based on their times of arrival, highlighted unexpected temporal aspects of complex DNA damage repair. The researchers could show that the proteins, which synthesize new stretches of DNA as part of the repair process, arrive at different times:

The proteins, which synthesize DNA without errors (error-free) are recruited within thirty seconds, while proteins performing imprecise DNA synthesis (error-prone) are recruited a minute later. The mechanism responsible for the delay in the error-prone synthesis, which is uncovered in this study, provides an opportunity for a precise repair of complex DNA damages.

The study also reveals that treatment with BMN673 (Talazoparib), a promising anticancer drug, dramatically changes the timescale of recruitment of DNA repair proteins at sites of complex damage. Notably, BMN673 delays the arrival of the error-free DNA synthesis machinery, which is loaded simultaneously with the error-prone repair proteins. The rearrangement in the order of the recruitment or removal of repair proteins as a result of BMN673 treatment, could affect the outcome of DNA repair and have a significant role for the anticancer activity of the drug.

The lead investigator Stoyno Stoynov from the IMB-BAS and former visiting scientist at the MPI-CBG and Alexander von Humboldt fellow at TU Dresden, concludes: ”This study generated a comprehensive kinetics-based resource which proved to be a powerful tool for investigating the interplay and coordination between DNA repair pathways. Even more importantly, it can serve as a platform for systematic evaluation of the effects of anticancer drugs targeting the DNA repair process.”

Aleksandrov, Radoslav et al. Molecular Cell, Volume 69 , Issue 6 , 1046 - 1061.e5
https://doi.org/10.1016/j.molcel.2018.02.016

About the MPI-CBG
The Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) is one of 84 institutes of the Max Planck Society, an independent, non-profit organization in Germany. 500 curiosity-driven scientists from over 50 countries ask: How do cells form tissues? The basic research programs of the MPI-CBG span multiple scales of magnitude, from molecular assemblies to organelles, cells, tissues, organs, and organisms.

About the IMB-BAS
The Institute of Molecular Biology is one of 42 institutes of the Bulgarian Academy of Sciences. IMB-BAS is the leading Bulgarian research institution in the area of molecular and cellular biology and biochemistry.

About the BIOTEC
The Biotechnology Center (BIOTEC) was founded in 2000 as a central scientific unit of the TU Dresden with the goal of combining modern approaches in molecular and cell biology with the traditionally strong engineering in Dresden. Since 2016 the BIOTEC is part of the central scientific unit “Center for Molecular and Cellular Bioengineering” (CMCB) of the TU Dresden.
The BIOTEC focuses on cell biology, biological physics, and bioinformatics.

Katrin Boes | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Further information:
https://www.mpi-cbg.de/de/home/

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

One step closer to reality

20.04.2018 | Life Sciences

The dark side of cichlid fish: from cannibal to caregiver

20.04.2018 | Life Sciences

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>