Protecting the genome: a novel protein helps prevent DNA damage caused by free radicals.

Macromolecules (DNA, proteins, and lipids) in all cells are constantly damaged by reactive oxygen species (ROS). In particular, ROS cause 1,000-7,000 DNA damages per day. Due to its lowest redox potential, the base guanine is mostly affected, resulting in the formation of 8-oxo-7,8-dihydroguanine. This modified base instructs incorporation of adenosine, instead of cytidine, by replicative DNA polymerases, potentially leading to GC ->TA transversion mutations. DNA polymerase lambda is the most efficient enzyme in performing accurate translesion synthesis over 8-oxo-7,8-dihydroguanine, since it preferentially incorporates the correct cytidine. In this paper we found that the protein called "DNA polymerase delta interacting protein 2" supports DNA polymerase lambda in its important task and can protect cells from ROS DNA damage. The next step will be to understand the regulation of PolDIP2 in normal vs. tumor cells. This study may help to better understand the mechanisms protecting cells from the accumulation of mutations, a process important in avoiding tumor transformation. Study funded by AIRC.

Reference: Maga G, Crespan E, Markkanen E, Imhof R, Furrer A, Villani G, Hubscher U, and van Loon B. (2013)DNA polymerase delta-interacting protein 2 is a processivity factor for DNA polymerase lambda during 8-oxo-7,8-dihydroguanine bypass. PNAS 2013 ; published ahead of print November 4, 2013, doi:10.1073/pnas.1308760110.