Histone degradation accompanies the DNA repair response

January 10, 2017
Histone degradation accompanies the DNA repair response
Credit: Friedrich Miescher Institute for Biomedical Research

Earlier work from the laboratory of Susan Gasser had noted changes in the physical behavior of chromatin when it incurred DNA damage: loci bearing double-strand breaks showed enhanced movement, becoming highly dynamic. Furthermore, the same effect could be observed with undamaged sites in a cell nucleus responding to DNA damage. Getting to the root cause of this phenomenon, Michael Hauer, a PhD student in her group discovered that histones dissociate from DNA and roughly 30% of the entire complement are degraded upon DNA damage. The process is controlled by the so-called checkpoint response, and the reduction in nucleosome density not only increases DNA mobility but also leads to increased chromatin accessibility for recombination-mediated repair.

DNA repair is paramount for the functioning of every cell and organism. Without it, proteins no longer work properly and genes are misregulated, all of which can lead to disease. It comes therefore as no surprise that the cell devotes enormous resources to detect and repair DNA damage and ensure DNA integrity.

Susan Gasser, Director of the Friedrich Miescher Institute for Biomedical Research, and her research group, have now identified a novel important process that safeguards DNA integrity. In a publication in Nature Structural and Molecular Biology, the scientists show that histone degradation upon DNA damage facilitates the repair processes.

Histones built up the spools around which DNA is wound and organized into chromatin, sometimes tighter, sometimes less tight. They define how accessible DNA is for the many proteins that interact with DNA, also the repair machinery. The scientist could now show in a sophisticated and elaborate study in yeast, that the cellular levels of histones drop by 20-40% in response to DNA damage. These histones are lost from DNA and are concomitantly degraded. As a consequence, chromatin is less compacted and becomes more flexible. They show that this in turn enhances repair by recombination mediated mechanisms.

"We think this newly elucidated process is an integral part of the DNA damage response," comments Susan Gasser. "The increased flexibility and mobility of the DNA allows the homology searches and accessibility for molecular interactions that are necessary for proper DNA ."

Michael Hauer adds: "We would now like to further see if this phenomenon of damage-induced histone degradation in yeast also holds true for higher organisms—will methods that can lower nucleosome occupancy in mammalian cells for example lead to increased rates of homologous recombination?"

Explore further: On the move for repair

More information: Michael H Hauer et al. Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates, Nature Structural & Molecular Biology (2017). DOI: 10.1038/nsmb.3347

Related Stories

On the move for repair

April 17, 2012

Scientists from the Friedrich Miescher Institute for Biomedical Research have elucidated mechanisms that control DNA movement in the nucleus. They found that DNA with double-strand breaks moves more than undamaged DNA, thereby ...

New functions for chromatin remodelers

August 28, 2014

Large molecular motors consisting of up to a dozen different proteins regulate access to the genome, which is essential for the transcription of genes and for the repair of DNA damage. Susan Gasser and her team now reveal ...

Laser pulses reveal DNA repair mechanisms

August 9, 2013

A new straightforward method enables monitoring the response of nuclear proteins to DNA damage in time and space. The approach is based on nonlinear photoperturbation.

Histone modifications control accessibility of DNA

July 14, 2010

(PhysOrg.com) -- n an advanced online publication in Nature Structural & Molecular Biology scientist from Dirk Schübeler's group from the Friedrich Miescher Institute for Biomedical Research provide a genome-wide view of ...

Recommended for you

These shrews have heads that shrink with the season

October 23, 2017

If any part of the body would seem ill equipped to shrink, it would probably be the head and skull. And, yet, researchers reporting in Current Biology on October 23 have found that the skulls of red-toothed shrews do shrink ...

Single-molecule dissection of developmental gene control

October 23, 2017

Scientists at EPFL and Max Plank have made significant discoveries on how developmental genes are controlled by the methyltransferase enzyme PRC2. The study is published in Nature Structural & Molecular Biology.

0 comments

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

Click here to reset your password.
Sign in to get notified via email when new comments are made.