DNA is the blueprint of life. Faithful replication of the genomic DNA is necessary which is carried by replicative DNA Polymerases (dPols). Based on sequence and structural homology, these enzymes are classified into seven families namely- A, B, C, D, X, Y and RT (Reverse Transcriptase). The members of X-family of DNA polymerases are generally involved in the Base excision repair (BER) and Non-homologous end joining (NHEJ) repair pathways. They exhibit low-processivity, low-fidelity and are capable of translesion synthesis. In my thesis work, I have carried out a biochemical examination of a representative member of the X-family from Staphylococcus aureus (named saPolX).
Unlike members of the X-family from eukaryotes, the enzymes from bacteria have an extra domain called Polymerase & Histidinol Phosphatase (PHP) domain. The PHP domain exhibits exonuclease and endonuclease activity. I have obtained data which shows that the exonuclease activity which is present in the PHP domain of SaPolX aids high fidelity DNA synthesis through the removal of mis- incorporated deoxyribo-, ribo- and oxidized nucleotides. Overall, my studies with saPolX provide novel insights into the strategies employed by PolX to execute faithful repair of DNA during BER pathways.
Reference:
Nagpal, S., & Nair, D. T. (2021). The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo-and oxidized nucleotides. Scientific reports, 11(1), 1-22.