Ionising radiation (IR) is capable of knocking off an electron from an atom, rendering high doses of it lethal to most living cells. To study the genetic basis of radiation resistance, scientists from the University of Wisconsin subjected the normally susceptible Escherichia coli to increasing levels of IR to develop a highly resistant variety.
Using a recently developed procedure, they were able to identify 46 genes that are generally not crucial for E. coli ’s survival, but become necessary when exposed to high levels of IR. The team believe that investigating these genes might help shed light on key pathways in humans that help protect us from cancer. “Humans have the same types of repair systems that bacteria do,” explained Michael M. Cox, one of the researchers, via email to this correspondent. “Because much larger numbers of cells can be generated and it is relatively easy to manipulate bacterial DNA and proteins, it is generally much easier to study bacterial enzymes than it is to study human ones.”
Exposure to IR can cause oxidative damage to the proteins in a cell, chemically alter DNA, and most crucially, lead to strand breakage.
Apart from obstructing replication, breakage of DNA strands can cause cells to become cancerous, especially if the break occurs within tumour suppressor genes.
The ability of some cells to resist IR was until now mainly attributed to their capacity to repair broken DNA and protect proteins from oxidative damage. However, Cox's study, published in Journal of Bacteriology this week, revealed that there are more mechanisms involved.
The team started with a library of radiation resistant E.coli cells. Each of the cells in the library then had a different gene inactivated by a method called Transposon Directed Insertion Sequencing (TraDIS). “If a particular gene is needed to recover from IR, all cells with insertions in that gene will die when subjected to IR,” said Cox via email.DNA repair functions
Out of the 46 genes-of-interest identified, 20 had DNA repair functions. The rest, however, were linked to not just protection from oxidation damage, but processes as varied as cell division control and cell wall maintenance.
The researchers are most excited about the 8 genes whose functions are yet unknown.
One of these genes, yejH, is significantly similar to a human gene called XPB. Efforts to investigate yejH’s role in DNA repair are ongoing. “The study of bacterial enzymes provides an important blueprint for future discovery in human cells, showing us where to look for the cellular components that are most important,” said Cox.