Researchers gain insight into mechanism underlying Huntington's
July 13, 2009Researchers 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 published today 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.
More information: http://www.nature.com/nsmb/index.html
Source: University of Kentucky
-
Biologists discover link between CGG repeats in DNA and neurological disorders
Jan 11, 2009 |
not rated yet |
0
-
Research breakthrough targets genetic diseases
Jan 20, 2009 |
not rated yet |
0
-
Researchers illuminate mechanisms that regulate DNA damage control and replication
Jan 05, 2009 |
not rated yet |
0
-
Discovery may result in new test to determine predisposition to cancer
Mar 25, 2009 |
not rated yet |
0
-
Researcher defines proteins that distinguish chromosome ends from DNA double-strand breaks
May 10, 2007 |
not rated yet |
0
-
Engineers build first sub-10-nm carbon nanotube transistor
Feb 01, 2012 |
4.9 / 5 (33) |
30
-
Something old, something new: Evolution and the structural divergence of duplicate genes
Jan 31, 2012 |
4.6 / 5 (7) |
1
-
The hidden nanoworld of ice crystals: Revealing the dynamic behavior of quasi-liquid layers
Jan 30, 2012 |
5 / 5 (5) |
1
-
Stock market network reveals investor clustering
Jan 27, 2012 |
3.9 / 5 (23) |
8
-
Of microchemistry and molecules: Electronic microfluidic device synthesizes biocompatible probes
Jan 26, 2012 |
5 / 5 (2) |
0
-
Factors affecting beet root cell membrane
22 hours ago
-
Stem cell question.
Feb 10, 2012
-
Protease cleavage
Feb 10, 2012
-
Pertubance in a model
Feb 10, 2012
-
Cancer drugs and Alzheimer's, Oh my!
Feb 09, 2012
-
Squishing cells
Feb 09, 2012
- More from Physics Forums - Biology
More news stories
New molecule has potential to help treat genetic diseases and HIV
(PhysOrg.com) -- Chemists at The University of Texas at Austin have created a molecule that's so good at tangling itself inside the double helix of a DNA sequence that it can stay there for up to 16 days before ...
46 minutes ago |
5 / 5 (2) |
0
|
Integrated pest management recommendations for the southern pine beetle
The southern pine beetle, Dendroctonus frontalis Zimmermann, is a chronic insect pest within pine forests in the southeastern United States. Under favorable environmental and host conditions, it is an agg ...
3 hours ago |
not rated yet |
0
A mitosis mystery solved: How chromosomes align perfectly in a dividing cell
Although the process of mitotic cell division has been studied intensely for more than 50 years, Whitehead Institute researchers have only now solved the mystery of how cells correctly align their chromosomes during symmetric ...
18 hours ago |
4.5 / 5 (22) |
0
|
Researchers find extensive RNA editing in human transcriptome
In a new study published online in Nature Biotechnology, researchers from BGI, the world's largest genomics organization, reported the evidence of extensive RNA editing in a human cell line by analysis of RNA-seq data, demons ...
18 hours ago |
5 / 5 (4) |
0
|
The proteins ensuring genome protection
Researchers from the University of Geneva (UNIGE), Switzerland, have discovered the crucial role of two proteins in developing a cell 'anti-enzyme shield'. This protection system, which operates at the level of molecular ...
18 hours ago |
5 / 5 (3) |
0
|
With climate change, today's '100-year floods' may happen every three to 20 years: research
Last August, Hurricane Irene spun through the Caribbean and parts of the eastern United States, leaving widespread wreckage in its wake. The Category 3 storm whipped up water levels, generating storm surges ...
Social psychologist: Lust makes you smarter and evidence that seven deadly sins are good for you
(Medical Xpress) -- Good news for lovers on Valentine’s Day - the seven deadly sins, including Lust, are good for you. University of Melbourne social psychologist Dr Simon Laham uses modern research to make a compelling ...
The joy of cheques
An electronic cheque which eliminates the need for costly processing by banks but preserves the simplicity and ease of a traditional cheque book has been designed by a team of academics in the UK.
Research shows promise in converting camelina oil into jet fuel
(PhysOrg.com) -- Researchers at Montana State University-Northern have developed a process to convert camelina oil to jet fuel and other high-value chemicals. MSU has applied for a U.S. patent and research is ongoing.
Couples in the same place emotionally stay together, study says
(Medical Xpress) -- Despite lifes ups and downs, couples whose feelings are in sync consistently over time are more likely to stay together, says a University of California, Davis, study.
Researchers make breakthrough in stem cell research
(Medical Xpress) -- University of Queensland scientists have developed a world-first method for producing adult stem cells that will substantially impact patients who have a range of serious diseases.