The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides
Abstract The 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-83498-1 |
| _version_ | 1830301894819446784 |
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| author | Shilpi Nagpal Deepak T. Nair |
| author_facet | Shilpi Nagpal Deepak T. Nair |
| author_sort | Shilpi Nagpal |
| collection | DOAJ |
| description | Abstract The 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. |
| first_indexed | 2024-12-19T08:57:44Z |
| format | Article |
| id | doaj.art-586cc13612b745c9bf32569a43cfe96b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:57:44Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-586cc13612b745c9bf32569a43cfe96b2022-12-21T20:28:34ZengNature PortfolioScientific Reports2045-23222021-02-0111112210.1038/s41598-021-83498-1The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotidesShilpi Nagpal0Deepak T. Nair1National Centre for Biological Sciences, Tata Institute of Fundamental ResearchRegional Centre for Biotechnology, NCR Biotech Science ClusterAbstract The 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.https://doi.org/10.1038/s41598-021-83498-1 |
| spellingShingle | Shilpi Nagpal Deepak T. Nair 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 |
| title | The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides |
| title_full | The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides |
| title_fullStr | The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides |
| title_full_unstemmed | The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides |
| title_short | The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides |
| title_sort | php domain of polx from staphylococcus aureus aids high fidelity dna synthesis through the removal of misincorporated deoxyribo ribo and oxidized nucleotides |
| url | https://doi.org/10.1038/s41598-021-83498-1 |
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