Oxidative stress is a frequent source of DNA damage. Apart from deoxyribonucleotides (dNMPs), cellular DNA polymerases (Pols) also incorporate ribonucleotides (rNMPs) during DNA synthesis. However, whether and how oxidative stress-triggered DNA repair synthesis leads to genomic rNMPs incorporation has not been known so far.
In collaboration with the group of Prof. Giovanni Maga in Pavia, Italy, the van Loon group has now discovered that specialized base excision repair (BER) Pols can bypass oxidative DNA damage by incorporating both dNMPs, as well as rNMPs. Interestingly, the incorporation of rNMPs opposite oxidized DNA bases negatively affects subsequent BER repair.
The study, which was published on February 26, 2016 in Nature Communications, suggests that besides during replication, rNMPs can be incorporated during DNA repair synthesis, in particular by Pol beta.