New study unravels mystery of a DNA repair process

March 14, 2012
Cell damaged by UVA light, as shown by the stripe, undergoing repair by enzymes

(Medical Xpress) -- Scientists at the University of Sussex have uncovered the mechanism of a key process in DNA repair that helps prevent neurodegenerative diseases such as ataxia.

A four-year study led by Dr. Sherif El-Khamisy at the Sussex Centre for Genome Damage and Stability, has focused on the behaviour of enzymes within cells that are involved in the repair of faults in DNA - the in our cells and all other .

The most common fault to occur spontaneously in DNA is single strand breaks (DNA being composed of two twisted strands). Failure to correct these breaks has been shown to lead to neurodegenerative disorders (those that attack the nervous system).

Previous research has shown that a particular enzyme,TPD1,is critical for repairing one type of these breaks, but it was not known how this enzyme reached sites of DNA damage. Now Dr El-Khamisy and his team have identified a peptide (a small protein composed of approximately 100 ) within cells, named SUMO, which helps bring TPD1 to the lesion to repair it.

This process is particularly important in cells that experience a high level of lesions and are unable to self-replicate, such as (neurons).

Dr. El-Khamisy said: “These findings were a surprise since it was known that this enzyme was important but it was an unresolved mystery as to how it reached the site of damage to deal with this kind of break.

“We were not expecting to find that this enzyme was modified by SUMO peptides, nor were we expecting to find that this modification helps to recruit this enzyme to the site of damage.” 

He said the results of this study, published this month in Nature Communications, will enhance the assessment of disorders such as the hereditary neurological disease, ataxia. “Addressing how these fascinating enzymes work will not only determine the importance of repairing for preventing neurodegenerative disease but might also identify novel markers for improving human health and promoting a healthy elderly population.”

The next step for Dr. El-Khamisy and his team is to look at environmental factors and drugs that affect this process, such as anti-cancer agents, ultra violet light, and radiation.

Explore further: Scientists identify protein that improves DNA repair under stress

More information: ‘SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair’, by Sherif  F El-Khamisy, et al, is published on March 13 in Nature Communications.

Related Stories

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 ...

Recommended for you

Natural compound reduces signs of aging in healthy mice

October 27, 2016

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency ...

A metabolic switch to turn off obesity

October 27, 2016

You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 ...

Scientists develop 'world-first' 3-D mammary gland model

October 27, 2016

A team of researchers from Cardiff University and Monash Biomedicine Discovery Institute has succeeded in creating a three-dimensional mammary gland model that will pave the way for a better understanding of the mechanisms ...

Mitochondria control stem cell fate

October 27, 2016

What happens in intestinal epithelial cells during a chronic illness? Basic research conducted at the Chair of Nutrition and Immunology at the Technical University of Munich (TUM) addressed this question by generating a new ...


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.