The Base Excision Repair Pathway in the Nematode Caenorhabditis elegans.

Noha Elsakrmy,Dindial Ramotar,Qiu-Mei Zhang-Akiyama

doi:10.3389/fcell.2020.598860

Abstract

Exogenous and endogenous damage to the DNA is inevitable. Several DNA repair pathways including base excision, nucleotide excision, mismatch, homologous and non-homologous recombinations are conserved across all organisms to faithfully maintain the integrity of the genome. The base excision repair (BER) pathway functions to repair single-base DNA lesions and during the process creates the premutagenic apurinic/apyrimidinic (AP) sites. In this review, we discuss the components of the BER pathway in the nematode Caenorhabditis elegans and delineate the different phenotypes caused by the deletion or the knockdown of the respective DNA repair gene, as well as the implications. To date, two DNA glycosylases have been identified in C. elegans, the monofunctional uracil DNA glycosylase-1 (UNG-1) and the bifunctional endonuclease III-1 (NTH-1) with associated AP lyase activity. In addition, the animal possesses two AP endonucleases belonging to the exonuclease-3 and endonuclease IV families and in C. elegans these enzymes are called EXO-3 and APN-1, respectively. In mammalian cells, the DNA polymerase, Pol beta, that is required to reinsert the correct bases for DNA repair synthesis is not found in the genome of C. elegans and the evidence indicates that this role could be substituted by DNA polymerase theta (POLQ), which is known to perform a function in the microhomology-mediated end-joining pathway in human cells. The phenotypes observed by the C. elegans mutant strains of the BER pathway raised many challenging questions including the possibility that the DNA glycosylases may have broader functional roles, as discuss in this review.

Highlights

Damage to the DNA is an inevitable process occurring persistently within a living cell
Of the eleven base excision repair (BER) DNA glycosylases conserved in humans, four are able to recognize uracil bases in the DNA, which can arise through cytosine deamination or as a result of misincorporation by a DNA polymerase (Whitaker et al, 2017)
We propose that C. elegans uracil DNA glycosylase-1 (UNG-1), unlike Ung from other organisms, may have evolved to acquire a broader substrate specificity and could act as the dominant DNA glycosylase in vivo to remove various modified forms of uracil such as the 5-hydroxymethyl uracil (5-hmU) lesion

Summary

The Base Excision Repair Pathway in the Nematode Caenorhabditis elegans

Excision Repair Pathway in the Nematode Caenorhabditis elegans. We discuss the components of the BER pathway in the nematode Caenorhabditis elegans and delineate the different phenotypes caused by the deletion or the knockdown of the respective DNA repair gene, as well as the implications. The DNA polymerase, Pol beta, that is required to reinsert the correct bases for DNA repair synthesis is not found in the genome of C. elegans and the evidence indicates that this role could be substituted by DNA polymerase theta (POLQ), which is known to perform a function in the microhomology-mediated endjoining pathway in human cells. The phenotypes observed by the C. elegans mutant strains of the BER pathway raised many challenging questions including the possibility that the DNA glycosylases may have broader functional roles, as discuss in this review

INTRODUCTION

Polymerase Q and Polymerase H

BER ENZYMES IN RELATION TO OTHER DNA REPAIR PATHWAYS

Link to MMR

Findings

Link to NER