Collisions of protein machines cause DNA replication derailment

February 24, 2011

Scientists have published results that will forever change the way researchers view the interplay between gene expression, DNA replication and the prevention of DNA damage.

DNA damage, if not kept in check, can lead to many problems including cancers. Researchers, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust and working at The University of Nottingham, have shown that the process of replication is even riskier than originally thought. This new information is published today (24 February) in the journal Nature.

Lead researcher Panos Soultanas, a Professor of Biological Chemistry from The University of Nottingham School of Chemistry said "Consider DNA as a bi-directional rail track with two types of train: a big fast one like an eight-carriage cross country train and a small slow one like a two-carriage regional train. As it travels, the big train - the DNA replisome - is responsible for copying the DNA e.g. when a cell is preparing to divide. And the small train - the RNA polymerase - makes its journey to deal with the expression of genes contained within the DNA sequence."

Just like trains, collisions between proteins moving along a strand of DNA can be catastrophic and this is one reason why areas of DNA that are being used a lot are particularly prone to damage. Until now it was thought that only head-on collisions between the DNA replisome (the big, fast, cross country train) and the RNA polymerase (the small, slow, regional train) could lead to serious DNA damage. This research shows that collisions between big and small trains running in the same direction can be just as dangerous and hence the problem in areas of high use is exacerbated.

Professor Soultanas said "Until now we thought that if the fast and slow protein-trains meet going in the same direction along the track then the faster DNA replication train just slows down and follows along behind the slower gene expression train until it has finished its job and moved out of the way. Our new research shows that this isn't the case at all and in fact they do collide quite often causing what, in this analogy, we could only describe as a major derailment!"

When the DNA replisome falls off the DNA there are other proteins - called "restart replication proteins" - that come in to help get it back on track. Although this ensures that DNA replication can continue, it can potentially increase the risk of mistakes occurring during the copying process, particularly if such restart replication proteins are malfunctioning. In some cases these mistakes can lead to problems e.g. if the mistake causes a genetic malfunction that can lead to a cancer developing.

Describing what happens to the DNA replisome in areas of DNA where there are many RNA Polymerases working on genes that are in high use, Professor Soultanas said: "We are now realizing that when there are a lot of slow moving trains close together on the track, the fast moving train is faced with a huge obstacle and any failure to safely negotiate these areas could easily result in significant errors. Therefore, replication restart mechanisms are of vital importance to ensure accurate copying of the genetic material"

Professor Douglas Kell, Chief Executive, BBSRC said "This is exciting news and an excellent achievement. Biological sciences as a discipline is unique because there are a collection of key ideas, tools, techniques and processes that are applied across an enormous range of topics. The interplay between gene expression, DNA replication and the prevention of DNA damage is an example of just such a tenet of biology and so this result has the potential to touch on research right across BBSRC's portfolio and beyond."
-end-


Biotechnology and Biological Sciences Research Council

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.