Author:
Nagpal Shilpi,Nair Deepak T.
Abstract
AbstractThe X family is one of the eight families of DNA polymerases (dPols) and members of this family are known to participate in the later stages of Base Excision Repair. Many prokaryotic members of this family possess a Polymerase and Histidinol Phosphatase (PHP) domain at their C-termini. The PHP domain has been shown to possess 3′–5′ exonuclease activity and may represent the proofreading function in these dPols. PolX from Staphylococcus aureus also possesses the PHP domain at the C-terminus, and we show that this domain has an intrinsic Mn2+ dependent 3′–5′ exonuclease capable of removing misincorporated dNMPs from the primer. The misincorporation of oxidized nucleotides such as 8oxodGTP and rNTPs are known to be pro-mutagenic and can lead to genomic instability. Here, we show that the PHP domain aids DNA replication by the removal of misincorporated oxidized nucleotides and rNMPs. Overall, our study shows that the proofreading activity of the PHP domain plays a critical role in maintaining genomic integrity and stability. The exonuclease activity of this enzyme can, therefore, be the target of therapeutic intervention to combat infection by methicillin-resistant-Staphylococcus-aureus.
Funder
Regional Centre for Biotechnology
Publisher
Springer Science and Business Media LLC
Reference79 articles.
1. Wu, W. J., Yang, W. & Tsai, M. D. How DNA polymerases catalyse replication and repair with contrasting fidelity. Nat. Rev. Chem. 1, 1–16 (2017).
2. Rudd, S. G., Bianchi, J. & Doherty, A. J. PrimPol—a new polymerase on the block. Mol. Cell. Oncol. 1, 1–10 (2014).
3. Rechkoblit, O. et al. Structure and mechanism of human PrimPol, a DNA polymerase with primase activity. Sci. Adv. 2, 1–8 (2016).
4. Ramadan, K., Shevelev, I. & Hübscher, U. The DNA-polymerase-X family: controllers of DNA quality?. Nat. Rev. Mol. Cell Biol. 5, 1038–1043 (2004).
5. Baños, B., Lázaro, J. M., Villar, L., Salas, M. & de Vega, M. Characterization of a Bacillus subtilis 64-kDa DNA polymerase X potentially involved in DNA repair. J. Mol. Biol. 384, 1019–1028 (2008).
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