Nucleic Acid Polymerases: The Two-Metal-Ion Mechanism and Beyond

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About this Research Topic

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Background

Polymerases are the nucleotidyl transferases that are responsible for synthesizing DNA and RNA. They are crucial for essential cellular processes including cellular and viral genome replication, DNA repair and damage tolerance, and transcription. Consistent with their vital roles, polymerases are found in all domains of life. The overall chemistry employed by these enzymes is conserved but there are variations among the different groups of polymerases that confer different substrate specificities and nucleotide incorporation fidelities that allow them to be involved in a wide array of cellular activities. Since polymerases were first isolated more than six decades ago, we have made great progress in understanding how different polymerases have adapted to their specific roles. In this Research Topic we will focus on the enzymatic mechanisms of these enzymes and the relationships between polymerase structure and mechanism, to highlight common themes and unique adaptations.

The aim of this Research Topic is to serve as a resource for the larger polymerase community, bringing together information about the large diversity present in this family of enzymes while also highlighting underlying common mechanisms. This will allow scientists working on different classes of polymerases to find a common platform to exchange ideas and build on each other’s experience and expertise. In addition, this Topic will contain historical perspectives about the progress we have made on decoding the enzymatic mechanisms of polymerases and point out the challenges that still remain in the field and how they can be tackled.

We will focus on reviews, original research articles, and perspectives that:

• Focus on the enzymatic mechanisms of cellular, organellar, and viral polymerases
• Relate polymerase structure to enzymatic mechanism
• Define how polymerases and terminal transferases achieve specificity for distinct substrates: incorporation of dNTP or rNTP nucleotides; DNA or RNA oligonucleotide primed synthesis, or primer-independent synthesis; use of DNA or RNA templates, or template-independent synthesis
• Describe how different polymerases have adapted their catalytic cycles for specific roles: rapid and high fidelity genome replication, repair synthesis, damage bypass, etc.
• Highlight how polymerase activities are altered when functioning within larger macromolecular complexes
• Provide a historical perspective on the development of different polymerase research fields
• Provide a perspective on future challenges and how avenues of progress in each area of polymerase research can inform the others

Dr. Satwik Kamtekar is currently an employee of Pacific Biosciences of California Limited and holds patents related to the theme of the Topic. All other Topic Editors declare no competing interests.

Keywords: Nucleic Acid Polymerases, two-metal-ion mechanism, polymerase, enzymatic mechanisms, cellular polymerases, organellar polymerases, viral polymerases

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