Navigation Links
Biologists discover link between CGG repeats in DNA and neurological disorders
Date:1/11/2009

MEDFORD/SOMERVILLE, Mass. Researchers have long known that some repetitive DNA sequences can make human chromosomes "fragile," i.e. appearing constricted or even broken during cell divisions. Scientists at Tufts University have found that one such DNA repeat not only stalls the cell's replication process but also thwarts the cell's capacity to repair and restart it. The researchers focused on this CGG repeat because it is associated with hereditary neurological disorders such as fragile X syndrome and FRAXE mental impairment.

In a study to be published in the January 2009 issue of the journal Nature Structural and Molecular Biology, Sergei Mirkin, White Family Professor of Biology at Tufts' School of Arts and Sciences, along with graduate students Irina Voineagu and Christine F. Surka and postdoctoral fellows Alexander A. Shishkin and Maria M. Krasilnikova, explored the link between CGG repeats and replication delays. Mirkin's research was funded by the National Institutes of Health.

Effect of palindromes

Past research from Mirkin's lab had shown that peculiar long DNA sequences named palindromes change the shape of the molecule from a double helix into a hairpin-like structure and, as a result, stall replication. When this happens chromosomes can break during cell division.

For the new research, Mirkin and his team analyzed different cloned CGG repeats in a mammalian cell culture line called COS-1 and in budding yeast cells. The researchers found that short triplets do not cause any problems. When the repeats got longer, however, the replication machinery got jammed and stalled in both systems. Thus, replication stalling likely accounts for the chromosomal fragility. They believe that this stalling is due to the formation of a stable, hairpin-like DNA structure formed by long CGG repeats.

Abnormal structures disable cellular checkpoints

"Our cells have evolved elaborate 'checkpoint' mechanisms to detect replication blocks and trigger the instant 'restart' of DNA replication there," said Mirkin. "Are the CGG repeats causing the checkpoints to fail?"

With replication stalled, Mirkin and his research team found that the CGG repeats did not respond to the key checkpoint protein called Mrc1 in yeast or claspin in humans. Both proteins work to repair replication malfunctions during the S phase of the cell cycle. Apparently, the unusual structure of CGG repeats acts to escape the cellular checkpoints. As a consequence, chromosomes under-replicate, become fragile and break.


'/>"/>

Contact: Alex Reid
alexander.reid@tufts.edu
617-627-4173
Tufts University
Source:Eurekalert

Related biology news :

1. Biologists learn structure, mechanism of powerful molecular motor in virus
2. Queens University biologists find new environmental threat in North American lakes
3. Biologists discover gene behind plant sex mystery
4. Caltech geobiologists discover unique magnetic death star fossil
5. Biologists, educators recognize excellence in evolution education
6. Caltech biologists spy on the secret inner life of a cell
7. Biologists identify genes controlling rhythmic plant growth
8. Biologists find diatom to reduce red tides toxicity
9. Model for angelman syndrome developed by University of Texas at Austin biologists
10. Caltech neurobiologists discover individuals who hear movement
11. Engineers create 3-D model to help biologists combat blue tongue virus
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/9/2017)... MELBOURNE , Australia , March ... clinical study data at the prestigious World Lung Imaging ... Dr. Andreas Fouras , was invited to deliver ... and pulmonary medicine. This globally recognised event brings together ... and share the latest developments in lung imaging. ...
(Date:3/6/2017)... MATEO, Calif. , March 6, 2017 /PRNewswire/ ... marketing and sales technology, today announced Predictive Sales ... solution for infusing actionable sales intelligence into Salesforce. ... to automatically enable their sales organizations with deep ... messages that allow for intelligent engagement. Predictive Sales ...
(Date:3/2/2017)... -- Australian stem cell and regenerative medicine company, ... agreement with the Monash Lung Biology Network, a consortia ... Department of Pharmacology at Monash University, Melbourne ... support the use of Cymerus™ mesenchymal stem cells (MSCs) ... is a chronic, long term lung condition recognised by ...
Breaking Biology News(10 mins):
(Date:3/22/2017)... --  iSpecimen ®, the marketplace for human ... (DPS), a full-service anatomic pathology reference lab serving ... , has joined a program offered by iSpecimen ... to make human biospecimens and associated data available to ... in 2015 as a collaboration between iSpecimen and DHIN, ...
(Date:3/22/2017)... 22, 2017   Boston Biomedical , an industry ... to target cancer stemness pathways, today announced its Board ... as Chief Executive Officer, effective April 24, 2017. ... Li , M.D., FACP, who has led Boston Biomedical ... his leadership, Boston Biomedical has grown from a "garage ...
(Date:3/22/2017)... ... March 21, 2017 , ... Proper ... information on the desired increase and/or decrease in antibody-dependent cellular cytotoxicity or complement-dependent ... profiling of therapeutic antibodies. , To meet this demand, the team at ...
(Date:3/22/2017)... ... March 21, 2017 , ... ... innovative Quantum peristaltic pump with patented ReNu single-use (SU) cartridge technology. Engineered ... for high-pressure feed pumps in SU tangential flow filtration (TFF), virus filtration ...
Breaking Biology Technology: