"Free oxygen radicals and a hybrid genome: a dangerous cocktail"

The genetic information is present in the cell as DNA, which is the form for storage and propagation to the next generation, and RNA, which is the form used by the cell to decode the instructions contained in its genes. DNA is composed of deoxynucleotides, while RNA is made of ribonucleotides. These two components are specifically recognised, respectively, by DNA polymerases, which use deoxynucleotides to build DNA, and by RNA polymerases, which synthesise RNA using ribonucleotides.
DNA polymerases are essential enzymes for DNA repair, being able to synthesise new fragments to replace those that have been damaged.
In a study published on Nature Communications, the group led by Dr. Giovanni Maga, at the Institute for Molecular Genetics CNR, in Pavia (Italy), in collaboration with the group led by Dr. Barbara van Loon at the University of Zürich, demonstrated that human DNA polymerases beta and lambda, essential for cellular tolerance towards oxidative stress (causing about 10,000 DNA lesions/per day/per cell), can mistakenly use ribonucleotides instead of deoxynucleotides. The result is a tract of hybrid genome, where DNA and RNA got mixed. The study also showed that these DNA/RNA hybrid genomic tracts, when damaged, are more difficult to be acted upon by other repair enzymes, actually promoting the accumulation of mutations. The results of this study may suggest that physiological oxidative stress tolerance systems by polymerases beta and lambda, in particular contexts, might contribute to the development of tumors or neurodegenerative diseases.
This study has been funded by the Italian Cancer Research Association AIRC.

Emmanuele Crespan, Antonia Furrer, Marcel Rösinger, Federica Bertoletti, Elisa Mentegari, Giulia Chiapparini, Ralph Imhof, Nathalie Ziegler, Shana J. Sturla, Ulrich Hübscher, Barbara van Loon and Giovanni Maga. Impact of ribonucleotide incorporation by DNA polymerases beta and lambda on oxidative base excision repair. Nature Comm. 2016, doi: 10.1038/ncomms10805