When DNA Polymerases Multitask: Functions Beyond Nucleotidyl Transfer.

Denisse Carvajal-Maldonado,Richard D Wood,Sylvie Doublié,Lea Drogalis Beckham

doi:10.3389/fmolb.2021.815845

Denisse Carvajal-Maldonado, Richard D Wood + Show 2 more

Open Access

https://doi.org/10.3389/fmolb.2021.815845

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Abstract

DNA polymerases catalyze nucleotidyl transfer, the central reaction in synthesis of DNA polynucleotide chains. They function not only in DNA replication, but also in diverse aspects of DNA repair and recombination. Some DNA polymerases can perform translesion DNA synthesis, facilitating damage tolerance and leading to mutagenesis. In addition to these functions, many DNA polymerases conduct biochemically distinct reactions. This review presents examples of DNA polymerases that carry out nuclease (3ʹ—5′ exonuclease, 5′ nuclease, or end-trimming nuclease) or lyase (5′ dRP lyase) extracurricular activities. The discussion underscores how DNA polymerases have a remarkable ability to manipulate DNA strands, sometimes involving relatively large intramolecular movement.

Highlights

DNA polymerases have been intensively studied for decades because of their fundamental importance in DNA replication
DNA polymerases catalyze the nucleotidyl transfer reaction to generate a DNA polymer. This class of enzymes is able to catalyze a host of other DNA processing reactions that make DNA polymerases a multi-tool of genomic integrity
Redundancy in the activities of DNA polymerases is critical for replication and maintenance of the cell

Summary

INTRODUCTION

DNA polymerases have been intensively studied for decades because of their fundamental importance in DNA replication. Organisms throughout nature possess an array of polymerases encoded by their genomes, specialized for functions in DNA repair, recombination, and DNA damage tolerance. The canonical DNA polymerase reaction is the addition of a nucleotide, usually a deoxynucleoside triphosphate, to the 3′ end of a growing DNA chain, liberating pyrophosphate (Figure 1). The reverse reaction, pyrophosphorolysis, catalyzed by some DNA polymerases, is driven backwards by an excess of pyrophosphate. The purpose of this review is to highlight the existence of additional activities associated with DNA polymerases beyond canonical nucleotidyl transfer (Figure 2). We briefly summarize each activity, emphasizing recent results and unsolved issues

39–59 Exonuclease Activity

CONCLUSION