Featured Research

from universities, journals, and other organizations

Insight Into Mechanism Underlying Huntington's Disease

Date:
July 15, 2009
Source:
University of Kentucky
Summary:
Researchers have gained new insight into the genetic mechanisms underlying Huntington's disease and other trinucleotide repeat (TNR) disorders, identifying a novel DNA repair pathway that specifically targets TNR hairpin removal in the daughter DNA strand.

Researchers at the University of Kentucky Markey Cancer Center and Graduate Center for Toxicology (GCT) have gained new insight into the genetic mechanisms underlying Huntington's disease and other neurodegenerative or neuromuscular disorders caused by trinucleotide repeats (or TNRs) in DNA.

The research, performed in the laboratory of Dr. Guo-Min Li, UK professor of toxicology and biochemistry and the Madeline James & Edith Gardner Distinguished Chair in Cancer Research, examined the mechanisms involved in the development of a specific type of genetic mutation known as trinucleotide repeat expansions. Diseases associated with these mutations, including Huntington's disease, are called trinucleotide repeat disorders.

Findings were just published in Nature Structural & Molecular Biology. GCT research scientist Caixia Hou, student Nelson Chan, and professor Liya Gu are coauthors of the study.

"Mutations – the genetic changes in DNA – can lead to many different types of disease, depending on where and in what manner they occur," Li said. "How these genetic changes escape normal DNA repair systems and become ingrained in an affected gene pool leading to familial disorders has been a longstanding subject of study in my laboratory at the UK Medical Center."

The expansion of TNRs at unique sites in the human genome is associated with at least 15 familial, neurodegenerative or neuromuscular disorders. The mechanism of TNR instability is poorly understood. However, because DNA expansions require DNA synthesis, DNA replication and/or DNA repair must be involved.

Two key TNRs, CAG and CTG repeats – associated with Huntington's disease and myotonic dystrophy, respectively – tend to form hairpin structures via strand slippage in the newly synthesized or "nicked" DNA strand during DNA synthesis associated with DNA replication and/or repair. These hairpin structures are highly thermo-stable and do not "melt" under normal physiologic conditions, and thus they are perceived as "fixed" in the DNA once formed, thereby leading to TNR expansions.

Using an extract of human cells, Li and his colleagues identified a novel DNA repair pathway referred to as DNA hairpin repair (HPR), which specifically targets TNR hairpin removal in the daughter DNA strand, ensuring the fidelity of the TNR sequences in the parental strand. It is proposed that defects or inadequacies in the HPR system may be responsible for TNR instability in the disease state.


Story Source:

The above story is based on materials provided by University of Kentucky. Note: Materials may be edited for content and length.


Cite This Page:

University of Kentucky. "Insight Into Mechanism Underlying Huntington's Disease." ScienceDaily. ScienceDaily, 15 July 2009. <www.sciencedaily.com/releases/2009/07/090713131603.htm>.
University of Kentucky. (2009, July 15). Insight Into Mechanism Underlying Huntington's Disease. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2009/07/090713131603.htm
University of Kentucky. "Insight Into Mechanism Underlying Huntington's Disease." ScienceDaily. www.sciencedaily.com/releases/2009/07/090713131603.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
More People Diagnosed With TB In 2013, But There's Good News

More People Diagnosed With TB In 2013, But There's Good News

Newsy (Oct. 22, 2014) The World Health Organizations says TB numbers rose in 2013, but it's partly due to better detection and more survivors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins