Knowledge of DNA repair mechanisms advances with new paper

May 11, 2017
Credit: Mayo Clinic

We humans like to think our DNA is well-protected in the nucleus of each cell. But it's a hard life for the hard-working genetic code.

DNA can be damaged by a range of normal cellular activities, not to mention ultraviolet light and ionizing radiation. The bad news is that damage, such as DNA double-strand breaks, is constantly occurring. But the good news is the human body has so-called damage response proteins to fix it.

Now, thanks to a new publication by Mayo Clinic researchers, scientists know more about these damage response proteins and how they do their job.

"This basic research is aimed at understanding how DNA damage response proteins work," explains Georges Mer, Ph.D., a Mayo Clinic biochemist. "We hope the knowledge gained from these studies might, in the long term, be beneficial from a therapeutic perspective, notably for cancer treatment."

Double-strand breaks

Certain types of radiation, such as gamma rays and X-rays, can cause breaks in both strands of DNA. If it's unfixable, the damage can trigger a cell to die. But Dr. Mer and team examined the way in which these breaks can trigger chemical signals to mobilize the DNA proteins.

Within the nucleus of the cell, DNA is wrapped around proteins called histones. A package of eight histones and DNA is called a . When a DNA double-strand break occurs, histones are chemically modified at different positions. The authors studied the modification that occurs when a molecule called ubiquitin attaches to a in response to the DNA break. They examined the attachment of ubiquitin on the H2A histone at two positions, and, when the call goes out, how the damage response protein attaches to the nucleosome.

"By deriving a detailed 3-D structure of [the damage response protein] RNF169 bound to the ubiquitylated nucleosome we explain how specificity is achieved in ubiquitin recognition," says Dr. Mer.

Expanded knowledge for future therapy

Many important regulatory interactions in the cell rely on recognition of ubiquitin-modified proteins. Structural studies like this one help define how ubiquitin is selectively recognized, as can be seen in the above image.

In this study, published in Molecular Cell, the authors also report that when RNF169, the DNA damage repair protein, binds to the nucleosome, it prevents another DNA repair protein from associating with the nucleosome. That other repair , 53BP1, shuts down an alternate pathway to repair DNA double-strand breaks. The authors note that inhibiting this inhibitor could, in principle, be exploited to reactivate this alternate DNA double-strand break pathway in cases where it is defective as in some forms of breast and ovarian cancer.

Explore further: Histone degradation accompanies the DNA repair response

Related Stories

Histone degradation accompanies the DNA repair response

January 10, 2017

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, ...

New switch decides between genome repair and death of cells

September 27, 2016

The genetic information of every cell is encoded in the sequence of the DNA double helix. Double strand breaks in the DNA, which can be induced by radiation, are a dangerous threat to the cells, and if not properly repaired ...

How breaks in DNA are repaired

February 2, 2017

A team of researchers from the biology department at TU Darmstadt has discovered that the processes for repairing DNA damage are far more complex than previously assumed. The ends of breaks in the double helix are not just ...

Molecular corkscrew

November 8, 2011

Scientists from the universities of Zurich and Duisburg-Essen have discovered a specific function of the protein p97/VCP. They demonstrate that the protein repairs DNA breaks like a corkscrew, a repair mechanism that could ...

Researchers discover new mechanism of DNA repair

July 3, 2015

The DNA molecule is chemically unstable giving rise to DNA lesions of different nature. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed.

Recommended for you

Scientists discover new plant in Shetland

August 16, 2017

Scientists at the University of Stirling have discovered a new type of plant growing in Shetland - with its evolution only having occurred in the last 200 years.

The irresistible fragrance of dying vinegar flies

August 16, 2017

Markus Knaden and Bill Hansson, and their colleagues at the Department of Evolutionary Neuroethology, study ecologically relevant odors in the natural environment of insects, especially vinegar flies. In this new study they ...

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.