About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Researchers Find Link Between DNA Transcription and Disease-Causing Expansions

by Bidita Debnath on November 26, 2014 at 9:48 PM
Font : A-A+

 Researchers Find Link Between DNA Transcription and Disease-Causing Expansions

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

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.

Advertisement

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."
Advertisement

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.

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Can Adjusting Fatty Acid Intake Improve Mood in Bipolar Disorder Patients?
Insulin Resistance Doubles the Risk of Major Depressive Disorder
Emotional Healing
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
DNA Finger Printing Genetic Testing of Diseases Epigenetics Oxidative Stress / Free Radicals Cell Injury 

Recommended Reading
Low-Cost DNA Sequencing Technology a Step Closer to Reality
At Arizona State University's Biodesign Institute and IBM's T.J. Watson Research Center, a team of ....
Multiple DNA 'Blind Spots' That may Hide Cancer-Causing Mistakes Uncovered
More than 400 'blind spots' in DNA which could hide cancer-causing gene faults have been identified ...
Abrupt Shifts in Disease Linked to Steadily Rising Increases in Mitochondrial DNA Mutations
The way in which subtle changes in mitochondrial function may cause a broad range of common ......
Smoking During Pregnancy Alters Newborn Stress Hormones and DNA
Newborns of mothers who smoke cigarettes during pregnancy show lower levels of stress hormones and ....
DNA Finger Printing
DNA fingerprinting is a technique which helps forensic scientists and legal experts solve crimes, id...
Epigenetics
In the recent years ‘epigenetics’ represents inheritable changes in gene expression that do not incl...
Genetic Testing of Diseases
Genetic testing helps to confirm a genetic condition in an individual and involves q complex laborat...
Oxidative Stress / Free Radicals Cell Injury
Oxidative stress is a form of injury to body tissues due to increase in free radicals. If the injur...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use