Scientists identify 'long distance scanner' for DNA damage

February 19, 2014
Scientists identify ‘long distance scanner’ for DNA damage
A DNA molecule in 3D

Scientists at the University of Bristol have discovered that a mechanism for preventing mutation within important genes involves long distance scanning of DNA by a molecular motor protein.

The results, published in the Proceedings of the National Academy of Sciences (PNAS), show that the method for detecting DNA damage within active genes is more sophisticated than previously thought.

The research team hope that the mechanistic insights provided by this study will help to explain the complicated genome-wide patterns of mutation that underlie the evolution of new species, also causing dangerous changes in cell behaviour.

The genetic information stored within the DNA of all living organisms contains the instructions which ensure cells function correctly. If the DNA is damaged, either by external agents such as the ultraviolet light present in sunshine or by chemical reactions that occur naturally within cells, the instructions can become corrupted by mutations.

Mutations that alter critical genes can lead to diseases such as cancer, or can enable pathogens such as bacteria to acquire new and dangerous characteristics such as antibiotic resistance.

Because the information within the DNA is so important, cells invest a huge amount of effort in repairing the damage before it can cause harm. But because damage is occurring continuously, and the cell does not have limitless resources, the repair activity must be targeted to the regions of greatest need.

When patterns of mutation are studied, it is clear that genes which are switched on are repaired first, with the inactive parts of the genome being repaired much more slowly.

Research over the past 20 years has shown that this two-tier system of repair relies on the ability of the molecular machines that read the active genes, called RNA polymerases, to sense the DNA damage and attract DNA repair systems to the problems that they have detected.

Researchers from the University of Bristol's School of Biochemistry have now shown that a molecular motor protein called Mfd - the first helper to be attracted by RNA polymerase when it gets into difficulties - acts as a long distance scanner for DNA damage.

Professor Nigel Savery, who led the group, said "Our results show that the method for detecting DNA damage within is more sophisticated than expected. The pathway that links DNA repair to gene expression has the potential to act over much greater distances than previously thought, because once it has been loaded onto the DNA by an RNA polymerase this first-response motor protein travels for hundreds of base pairs - the building blocks of the DNA double helix - in search of damage.

"Our work also provides the first indication that sequences of DNA where RNA polymerases briefly slow down and pause may be acting as signals for the DNA repair proteins to scrutinise the neighbouring DNA particularly carefully."

Explore further: Protecting genes, one molecule at a time

More information: 'Stalled transcription complexes promote DNA repair at a distance' by N.Haines, Y. T. Kim, A. J. Smith, N. J. Savery in PNAS.

Related Stories

Protecting genes, one molecule at a time

September 9, 2012
An international team of scientists have shown at an unprecedented level of detail how cells prioritise the repair of genes containing potentially dangerous damage. The research, published in the journal Nature and involving ...

Novel cancer cell DNA damage repair mechanism unveils

December 10, 2013
Research with a Finnish background facilitates the development of more effective cancer medication

Potential biomarkers for the diagnosis of Alzheimer's disease

January 31, 2014
Researchers identify abnormal expression of genes, resulting from DNA relaxation, that can be detected in the brain and blood of Alzheimer's patients.

A protein's role in helping cells repair DNA damage

November 1, 2012
(Medical Xpress)—In a new study, University at Buffalo scientists describe the role that a protein called TFIIB plays in helping cells repair DNA damage, a critical function for preventing the growth of tumors.

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.