Resilience through improvisation

Our cells are resourceful when it comes to copying DNA, even when the DNA is damaged

Billions of cells divide every day in our bodies to replace those that wear out. To be able to do so, their DNA must be copied. A new Weizmann Institute study shows that the molecules in charge of the task of copying DNA — called DNA polymerases — are able to improvise in order to achieve this crucially important goal. This new insight into DNA replication and repair could assist in the diagnosis and treatment of diseases in which DNA damage is involved, such as cancer. The surprising findings appear in the December 9 issue of Proceedings of the National Academy of Sciences (PNAS), USA.

DNA polymerases travel along the DNA, producing new “printouts” of it each time the cell divides. In this way, genetic information is passed on in our bodies and from generation to generation. However, problems begin when the DNA is damaged due to factors such as cigarette smoke, radiation and certain reactions in the body. Though our body possesses special enzymes that fix DNA, some damage escapes their notice — and DNA polymerases must deal with it.

Prof. Zvi Livneh and Ph.D. student Ayelet Maor-Shoshani of the Biological Chemistry Department cut a DNA strand — from the bacterium E. coli — and inserted material similar to that which composes crude oil in between both its ends. As expected, the regular DNA polymerase stopped working when it reached the foreign material. Yet to the scientists’ amazement, a specialized DNA polymerase jumped in to rescue the stalled replication process, and continued the copying process, inserting nonexistent genetic components into the “printout” when it encountered the foreign material. This can be compared to a person who forgets some words in a song and makes up new ones to be able to continue to sing.

In other cases, the specialized DNA polymerase skipped over the foreign material or deleted it and thus was able to continue its work as usual. “This shows the remarkable capability of a cell to reproduce,” says Livneh. “And it makes one hope that even if extreme types of chemicals are accidentally introduced into our DNA, the body will be able to manage.”

True, when DNA polymerase improvises a tune, errors (i.e. mutations) may occur in the new cells’ DNA. Yet Livneh explains that the body cannot feasibly let all cells with damaged DNA die, for there are too many of them. “Only if the DNA contains a very high level of damage will the cell’s machinery ’give up’ and let the cell die.”

Prof. Zvi Livneh’s research is supported by the M.D. Moross Institute for Cancer Research, the Levine Institute of Applied Science, the Dr. Josef Cohn Minerva Center for Biomembrane Research, the Dolfi and Lola Ebner Center for Biomedical Research, and the J & R Center for Scientific Research. Prof. Livneh is the incumbent of the Maxwell Ellis Professorial Chair in Biomedical Research.