Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.18.303297v1?rss=1 Authors: Balint, E., Unk, I. Abstract: Polymerase eta (Pol{eta}) is a translesion synthesis DNA polymerase directly linked to cancer development. It can bypass several DNA lesions thereby rescuing DNA damage-stalled replication complexes. We previously presented evidence implicating Saccharomyces cerevisiae Pol{eta} in transcription elongation, and identified its specific RNA extension and translesion RNA synthetic activities. However, RNA synthesis by Pol{eta} proved rather inefficient under conditions optimal for DNA synthesis. Searching for factors that could enhance its RNA synthetic activity, we have identified the divalent cation of manganese. Here we show, that manganese triggers drastic changes in the activity of Pol{eta}. It increases the efficiency of ribonucleoside incorporation into RNA by ~400-2000-fold opposite undamaged DNA, and ~3000 and ~6000-fold opposite TT dimer and 8oxoG, respectively. Importantly, preference for the correct base is maintained with manganese during RNA synthesis. In contrast, activity is strongly impaired, and base discrimination almost lost during DNA synthesis by Pol{eta} with manganese. Moreover, Pol{eta} shows strong preference for manganese during RNA synthesis even at 25-fold excess magnesium concentration. Based on these, we suggest that selective metal cofactor usage plays an important role in determining the specificity of Pol{eta} during synthesis enabling it to function at both replication and transcription. Copy rights belong to original authors. Visit the link for more info