Cellular DNA is constantly exposed to endogenous and exogenous damaging agents, such as free oxygen radicals, UV light and carcinogenic pollutants. The resulting chemical modifications of DNA bases, alter the genetic information contained in the cellular genome, causing mutations. Cells have evolved specialized enzymes, the so called translesion DNA polymerases, capable of retrieving the correct information from damaged DNA. Failure or misregulation of these mechanisms can lead to cancer. The group led by Dr. Giovanni Maga, at the IGM-CNR in Pavia, in collaboration with the group of Prof. Ulrich Hubscher at the University of Zürich, has discovered that the human translesion DNA polymerase lambda uses a small inorganic phosphate compound, pyrophosphate, as an essential cofactor for increasing its ability to produce a fatihful copy of the original information coded by a damaged DNA base. Pyrophosphate is a byproduct of many metabolic reactions and these results show, for the first time, its role as an essential cofactor for the maintenance of genomic stability of the cells. This research has been funded by the Italian Association for Cancer Research (AIRC)
Crespan E, Maga G, Hübscher U. A new proofreading mechanism for lesion bypass by DNA polymerase-lambda. EMBO Rep. 2011 Dec 23;13(1):68-74. doi: 10.1038/embor.2011.226.
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