DNA Damage Tolerance by Eukaryotic DNA Polymerase and Primase PrimPol.

Elizaveta O Boldinova,Paulina H Wanrooij,Evgeniy S Shilkin,Alena V Makarova,Sjoerd Wanrooij

doi:10.3390/ijms18071584

Abstract

PrimPol is a human deoxyribonucleic acid (DNA) polymerase that also possesses primase activity and is involved in DNA damage tolerance, the prevention of genome instability and mitochondrial DNA maintenance. In this review, we focus on recent advances in biochemical and crystallographic studies of PrimPol, as well as in identification of new protein-protein interaction partners. Furthermore, we discuss the possible functions of PrimPol in both the nucleus and the mitochondria.

Highlights

Human cells contain a variety of deoxyribonucleic acid (DNA) polymerases that differ in function and fidelity
Multisubunit replicative DNA polymerases Pol δ and Pol ε possess high fidelity and play a pivotal role in the replication of genomic DNA due to the stringent requirements of their active site [1], while Pol α, which forms a complex with primase, is responsible for the initiation of DNA replication during de novo ribonucleic acid (RNA)-primer synthesis at the origins of replication [2,3]
Lesion bypass can be error-free or error-prone depending on the type of lesion and the particular translesion DNA polymerase that is involved in synthesis

Summary

Introduction

Human cells contain a variety of deoxyribonucleic acid (DNA) polymerases that differ in function and fidelity. Prim belongs to the archaea-eukaryotic primase (AEP) superfamily Many members of this superfamily possess both primase and DNA polymerase activities and play an essential role in initiation of DNA replication, and undertake a wide variety of cellular roles in DNA replication, damage tolerance and repair, in addition to primer synthesis [24]. In 2012 and 2013, this new enzyme was purified and characterized as a translesion DNA polymerase with low accuracy of DNA synthesis and primase activity. It was initially presented by the L. PrimPol-related proteins were not identified in such common model organisms as Drosophila melanogaster, Caenorhabditis elegans and Saccharomyces cerevisiae

Activities and Fidelity of PrimPol

The Role of PrimPol in Nuclear Replication and DNA Translesion Synthesis

Functions of PrimPol in Mitochondria

Regulation of PrimPol Activity in Cells

PrimPol Dysfunction and Disease

Conclusions