First-ever look at DNA opening reveals initial stage of reading the genetic code

June 2, 2017 by Hayley Dunning
Proteins interacting with the DNA strand. Credit: Imperial College London

Scientists have watched a cell's genetic machinery in the first stages of 'reading' genes, giving a potential way to stop the process in bacteria.

By reading certain genes - a process known as transcription - cells can produce and regulate proteins, which perform almost all the functions necessary for life.

In the new study, researchers used an extremely powerful technique called cryo-electron microscopy to physically see how this process happens in detail, for the first time. The insights could help researchers target this stage of transcription in with new antibiotics.

DNA is composed of two strands, which are normally linked together in a twisted helical structure. The strands are pulled apart by several specialist molecules that 'melt' it – preventing the strands from coming back together as they normally try to do. This step in transcription usually happens very quickly, with a lot of changes occurring over a short time span, meaning it has been impossible to track in detail before.

In the study published today in Molecular Cell, the research team led by scientists at Imperial College London viewed the DNA opening in action.

Since transcription of DNA is so fundamental to the functioning of a cell, the team believe that knowing how it operates in bacteria could provide avenues for blocking the process, potentially shutting down the actions of harmful infections.

New ways to stop bacteria

Lead researcher Professor Xiaodong Zhang, from the Department of medicine at Imperial, said: "Bacteria are becoming increasingly resistant to antibiotics, so our insights into the first stage of transcription provide new ways of thinking about stopping bacteria.

"Understanding how the fundamental machinery works hopefully gives us additional tools for developing new kinds of antibiotics. As we investigate more steps in the process of transcription, we may find more stages during which we can intervene and attack ."

The process of transcription occurs in all living things and plays a crucial role in many cellular processes, including those related to diseases like cancer. The new insights might therefore apply across a whole range of organisms and disease processes.

Activating transcription

In particular, the team studied the action of a called sigma54, which controls a wide range of bacterial defences, holding them back until they need to be used. If drugs could be designed to interfere with this step, and preserve sigma54's power to hold back defences, they could make bacteria more vulnerable to attack.

Sigma54 unleashes the bacterial defences after being activated by a protein that changes sigma54's shape. The 'activator' protein, together with sigma54, then forms a protein wedge that drives the two DNA strands apart. The bacterial defence genes are then read and kicked into action.

The researchers were able to watch this in detail, giving them new insights into how they might use sigma54 to disable the bacteria's defences.

Study co-author Professor Martin Buck, from the Department of Life Sciences at Imperial, said: "DNA contains genetic information, which is converted to proteins that carry out all cell functions. Transcription is the first stage in accessing that information.

"It underpins all environmental adaptation in organisms – it's how cells deal with their changing environments or even become abnormal, such as in cancer . Our work could therefore have implications across a range of biological processes."

Explore further: Discovery of trigger for bugs' defenses could lead to new antibiotics

More information: Robert Glyde et al. Structures of RNA Polymerase Closed and Intermediate Complexes Reveal Mechanisms of DNA Opening and Transcription Initiation, Molecular Cell (2017). DOI: 10.1016/j.molcel.2017.05.010

Related Stories

Recommended for you

Gene editing in the brain gets a major upgrade

October 19, 2017

Genome editing technologies have revolutionized biomedical science, providing a fast and easy way to modify genes. However, the technique allowing scientists to carryout the most precise edits, doesn't work in cells that ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

BEGINNING
1 / 5 (1) Jun 02, 2017
Fact: In all known cases, codes and coded information are always the result of an intelligent source.

Fact: The production and reproduction of life depends on the most complex, dense and miniaturized codes and coded information known to man.

Fact: the whole scientific community cannot understand the huge ammounts of DNA coded information.

Fact: codes and coded information are imaterial meanings ascribed to sequences of symbols (vg. A, T, G, C) and not matter or energy.

Fact: There is no natural law or physical process able to create meaningful codes and coded information.

Fact: There is no viable naturalistic explanation for the origin of life.

Fact: the molecular machines that transcribe, read and execute DNA coded information are thenselves coded in DNA.

Fact: random mutations are cumulative and degerative creating "noise", degrading information and causing disease, cancer, suffering and death.
Captain Stumpy
not rated yet Jun 05, 2017
@beginning to demonstrate lunacy with your idiocy
Fact: random mutations are cumulative and degerative creating "noise", degrading information and causing disease, cancer, suffering and death
Fact: you're an illiterate idiot religious looney

actually, that whole "degerative"[sic] stupidity you posted is a load of crap, and i didn't even bother to read anything else because it's so religiously delusional it's just pathetic

(see link below proving you wrong... mind you, it's not suggesting, positing, guessing or hypothesizing, nor is it potentially possible or being mathematically suggested; it's actual physical replicated validated irrefutable proven fact that you're wrong)

http://myxo.css.m...dex.html

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.