Structural knowledge of the DNA repair complex – Phys.Org

March 21, 2017 by Lisbeth Heilesen A model for monitoring and repairing damaged DNA (left figure). The crystal structure of the DNA control protein Rad26 that is responsible for bringing the Rad3 kinase to damaged DNA and starting repair signalling (right figure). Credit: Kasper Rjkjr Andersen

New Danish research provides mechanistic insight into how DNA is monitored and repaired if damage occurs. The results may eventually help to improve the treatment of certain types of cancer, as the DNA repair complex provides a mechanism for cancer cells to resist chemotherapy.

Our DNA is constantly exposed to damage and to protect the genome, cells have evolved mechanisms that monitor and repair these damages. Our structural knowledge of the protein complexes that monitor DNA has so far been limited. New research now describes the structure and organisation of the DNA controls protein Rad26 and shows how the kinase Rad3 is recruited to sites of damaged DNA.

To maintain the genome integrity, DNA damages have to be monitored and repaired. The first step in this process is orchestrated by the Rad3 kinase. Rad26 is a functional subunit of Rad3-rad26 DNA repair complex and is responsible for bringing the kinase to sites of DNA damage, but the mechanism behind kinase recruitment and structural knowledge of how this complete is organized has until now been unclear.

New results from Aarhus reveal the crystal structure of Rad26 and identify the elements that are important for recruiting Rad3 kinase. Rad26 is a dimer with a conserved interface in the N-terminal part of the protein. Biochemical data demonstrated that Rad26 uses its C-terminal domain and a conserved motif to recruit Rad3. From the in vitro reconstituted Rad3-Rad26 complex, small-angle X-ray scattering and electron microscopic studies, it is possible to model the quaternary structure and thus bring us closer to a mechanistic understanding Rad3-Rad26 DNA repair apparatus.

Rad3 signalling ensures that cells do not divide before DNA damages are repaired and thus provides cancer cells with a mechanism to resist chemotherapy by repairing these DNA damages. Our new structural knowledge will help the development of Rad3 inhibitors that make cancer cells more susceptible to chemotherapy and this new treatment is now being tested in clinical trials.

The study is published in The Journal of Biological Chemistry.

Explore further: Researchers probe a DNA repair enzyme

More information: Kasper Rjkjr Andersen. Insights into Rad3 kinase recruitment from the crystal structure of the DNA damage checkpoint protein Rad26, Journal of Biological Chemistry (2017). DOI: 10.1074/jbc.M117.780189

Researchers have taken the first steps toward understanding how an enzyme repairs DNA. Enzymes called helicases play a key role in human health, according to Maria Spies, a University of Illinois biochemistry professor.

Researchers at the University of Copenhagen have discovered a molecular mechanism that reads so-called epigenetic information and boosts repair of lesions in our DNA. This knowledge can be used to develop new targeted cancer ...

DNA double-strand breaks (DSBs) are the worst possible form of genetic malfunction that can cause cancer and resistance to therapy. New information published this week reveals more about why this occurs and how these breaks ...

The occurrence of chemotherapy resistance is one of the major reasons for failure in cancer treatment. A study led by scar Fernndez-Capetillo, Head of the Genomic Instability Group at the Spanish National Cancer Research ...

A protein that helps embryonic stem cells (ESCs) retain their identity also promotes DNA repair, according to a study in The Journal of Cell Biology. The findings raise the possibility that the protein, Sall4, performs a ...

A group of researchers at Osaka University found that if DNA damage response (DDR) does not work when DNA is damaged by radiation, proteins which should be removed remain instead, and a loss of genetic information can be ...

University of Sydney researchers have used infrared spectroscopy to spotlight changes in tiny cell fragments called microvesicles to probe their role in a model of the body's immunological response to bacterial infection.

Zinc is a vital micronutrient involved in many cellular processes: For example, in learning and memory processes, it plays a role that is not yet understood. By using nanoelectrochemical measurements, Swedish researchers ...

Whether inside your laptop computer or storing energy outside wind farms, we need high-capacity, long-lasting, and safe batteries. In batteries, as in any electrochemical device, critical processes happen where the electrolyte ...

Photoreceptors in vertebrates typically consist of two separate colourless parts: an organic pigment and a protein. Combined, they create a colourful, light-sensitive molecule called an iminium ion that triggers vision upon ...

Borrowing from nature is an age-old theme in science. Form and function go hand-in-hand in the natural world and the structures created by plants and animals are only rarely improved on by humans.

Prion diseases are scary, incurable and fatal. They first gained notoriety when cows became infected by prion proteins and, in turn, infected people. Fervor surrounding mad cow disease resulted in the U.S. banning imports ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See the original post here:
Structural knowledge of the DNA repair complex - Phys.Org