Gurdon Institute research uncovers new genes responsible for genome stability
A five-year round-the-clock project has yielded new insights into how DNA is kept stable in cells.
Researchers at the Gurdon Institute at the University of Cambridge have created a unique resource through the work that will help functional genomics studies around the world.
Stability of the genome is key for all living organisms for their maintenance and reproduction.
Some genes are known to have a role in regulating this stability - preventing or correcting DNA errors, for example.
Changes in the number of repetitive DNA sequences, or the loss of parts of genes, or whole chromosomes, can lead to cell dysfunction or death.
The team in the laboratory of Steve Jackson used an important research resource - the Saccharomyces cerevisiae Yeast Knockout Collection - to study the impact of each single gene in maintaining genome stability.
Each individual strain in the collection has had one gene that is not essential for life 'knocked out' - meaning it has been removed.
Until now, each strain’s full DNA sequence was not available. But the researchers systematically applied next-generation sequencing to all 4,500 of them, then found, measured and catalogued changes in the genome caused by each single knockout.
They uncovered new genes responsible for maintaining the stability of DNA in cells, and whose absence or mutation leads to various effects, from changes in short sequence repeats to the loss of whole chromosomes.
In humans, such mutational signatures, are connected to disease and ageing. They can now also be studied in human cells, which contain genes with similar functions.
Prof Jackson said: “We knew about some of these ‘genome instability’ genes already, but this systematic project has uncovered many new ones that affect genome stability.
“It has also identified new types of mutational signatures, such as variations in the number of repetitive elements, loss or gain of chromosomes in whole or part, and alterations in mitochondrial DNA copy-number.”
Postdoc Dr Fabio Puddu, the paper's lead author, added: “This study is one of its kind. It will help us and others around the world who use the Yeast Knockout Collection for functional genomic studies, and it is already paving the way for follow-on investigations, in both yeast and human cells.”
The resource is freely available at http://sgv.gurdon.cam.ac.uk.