Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A link between DNA transcription and disease-causing expansions

26.11.2014

Researchers in human genetics have known that long nucleotide repeats in DNA lead to instability of the genome and ultimately to human hereditary diseases such Freidreich's ataxia and Huntington's disease.

Scientists have believed that the lengthening of those repeats occur during DNA replication when cells divide or when the cellular DNA repair machinery gets activated. Recently, however, it became apparent that yet another process called transcription, which is copying the information from DNA into RNA, could also been involved.

A Tufts University study published online on November 20 in the journal "Cell Reports" by a research team lead by Sergei Mirkin, the White Family Professor of Biology at Tufts' School of Arts and Sciences, along with former graduate student Kartick Shah and graduate students Ryan McGuity and Vera Egorova, explores the relationship between transcription and the expansions of DNA repeats. It concludes that the active transcriptional state of a DNA segment containing a DNA repeat predisposes it for expansions. The print version of the study will be published on December 11.

"There are a great many simple repetitive motifs in our DNA, such as GAAGAAGAA or CGGCGGCGG," says Mirkin. "They are stable and cause no harm if they stay short. Occasionally, however, they start lengthening compulsively, and these uncontrollable expansions lead to dramatic changes in genome stability, gene expression, which can lead to human disease."

In their study, the researchers used baker's yeast to monitor the progress and the fundamental genetic machineries for transcription, replication and repair in genome functioning.

"The beauty of the yeast system is that it provides one with a practically unlimited arsenal of tools to study the mechanisms of genome functioning," says Mirkin. "We created genetic systems to track down expansions of the repeats that were positioned in either transcribed or non-transcribed parts of reporter genes."

After measuring the rate of repeat expansions in all these cases, the authors found that a repeat can expand under the condition when there is practically no transcription, but the likelihood of the expansion process is drastically (10-fold) higher when the reporter is transcriptionally active.

Surprisingly, however, transcription machinery does not need to physically pass through the repeat to stimulate its expansion. Thus, it is the active transcription state of the repeat-containing DNA segment, rather than RNA synthesis through the repeat that promotes expansions.

In the transcriptionally active state, DNA is packaged in chromatin more loosely than when it is transcriptionally inactive. More specifically, the density of nucleosomes along the transcribed DNA segment is significantly lower than that in the non-transcribed segment. This packaging of repetitive DNA within the transcribed areas gives much more room for DNA strand gymnastics, ultimately leading to repeat expansions.

Whatever the exact model, says Mirkin, the fact that expandable DNA repeats were always found in transcribed areas of our genome may not be that surprising after all.

This study was funded by NIH grants GM60987 and GM105473.

Shah et al., 2014, Cell Reports 9, 1-9
December 11, 2014
http://dx.doi.org/10.1016/j.celrep.2014.10.048

Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the Premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university's schools is widely encouraged.

Alex Reid | EurekAlert!
Further information:
http://www.tufts.edu/

More articles from Health and Medicine:

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

nachricht Prospect for more effective treatment of nerve pain
20.02.2017 | Universität Zürich

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>