In a Nature paper published yesterday, Baylor College of Medicine researchers report that in E. coli, the fidelity of transcribing DNA is more important to a cell than DNA repair.
"If you asked a group of scientists which is more important for a cell, maintaining the integrity of its DNA containing all of the organism's genetic information, or the fidelity of transcription—the process that transcribes DNA into RNA, which leads to protein synthesis—the vast majority would agree that repairing DNA is more important," said corresponding author Christophe Herman, Ph.D., associate professor of molecular and human genetics and molecular virology and microbiology at Baylor. "In this study, we show the opposite."
Herman's lab has been studying the fidelity of transcription for a number of years and has shown that transcription errors can actually lead to heritable change. This made them think that perhaps transcription fidelity was actually more important than previously anticipated. So in this study, the researchers investigated what would happen if they removed GreA, a factor that helps ensure the fidelity of the transcription process on the bacterium E. coli, on DNA break repair.
"After removing GreA, bacteria were hundreds of times more efficient at repairing DNA damage caused by drugs that mimic radiation," said first author Priya Sivaramakrishnan, Ph.D., a student in the Herman lab during the development of this project. "Bacteria can repair DNA breaks much faster when GreA is absent."
To figure out how GreA lead to faster repairs, the researchers used a whole-genome sequencing method that they named eXOnucleases sequencing, to visualize the different steps of DNA repair in living cells. With this and other methods, the researchers were able to determine how losing GreA promotes DNA repair. This finding surprised the scientists because it implies that ensuring proper transcription fidelity even comes at the cost of lowering the cell's ability to repair DNA.
"The conservation of the basic biology of nucleic acids from bacteria to humans is tremendous. We hypothesize that this mechanism discovered in E. coli might also be present in other cells, which would have implications in a number of fields, from cancer to evolution," said Susan Rosenberg, Ph.D., Ben F. Love Chair in Cancer Research and professor of molecular and human genetics, of molecular virology and microbiology and of biochemistry and molecular biology at Baylor.