Abstract

DNA replication is arguably the most fundamental biological process. On account of their shared evolutionary ancestry, the replication machinery found in archaea is similar to that found in eukaryotes. DNA replication is initiated at origins and is highly conserved in eukaryotes, but our limited understanding of archaea has uncovered a wide diversity of replication initiation mechanisms. Archaeal origins are sequence-based, as in bacteria, but are bound by initiator proteins that share homology with the eukaryotic origin recognition complex subunit Orc1 and helicase loader Cdc6). Unlike bacteria, archaea may have multiple origins per chromosome and multiple Orc1/Cdc6 initiator proteins. There is no consensus on how these archaeal origins are recognised—some are bound by a single Orc1/Cdc6 protein while others require a multi- Orc1/Cdc6 complex. Many archaeal genomes consist of multiple parts—the main chromosome plus several megaplasmids—and in polyploid species these parts are present in multiple copies. This poses a challenge to the regulation of DNA replication. However, one archaeal species (Haloferax volcanii) can survive without replication origins; instead, it uses homologous recombination as an alternative mechanism of initiation. This diversity in DNA replication initiation is all the more remarkable for having been discovered in only three groups of archaea where in vivo studies are possible.

Highlights

  • The principles of DNA replication are common across all three domains of life—bacteria, archaea, and eukaryotes—but there is a fundamental split in terms of the machinery used [1]

  • Similar to the bacterial origins of replication, archaeal replication origins have a clearly defined structure consisting of an AT-rich DNA unwinding element (DUE) flanked by several conserved repeats termed origin recognition boxes (ORBs) that serve as binding sites for the origin recognition protein(s)

  • A similar case was observed in Pyrococcus abyssi where Orc1/Cdc6 remains bound to the replication origin both in the exponential and stationary phases, while minichromosome maintenance (MCM) is associated with the origin only in the exponential phase [35]

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Summary

Introduction

The principles of DNA replication are common across all three domains of life—bacteria, archaea, and eukaryotes—but there is a fundamental split in terms of the machinery used [1]. Studies of archaeal DNA replication have focused on the biochemical characterization of key enzymes involved in DNA synthesis and, despite the recognized diversity of archaeal domain, have been limited to few species. This is understandable given the interest in exploiting extremophilic enzymes in biotechnology and the difficulty of generating genetic tools for most archaeal species (see Figure 1). DNA replication initiation is the key regulatory stage for the processes of DNA replication and the cell cycle, and the most powerful methods to study the regulation of DNA replication initiation rely on in vivo genetic analysis These are available for only three groups of archaea: Sulfolobales, Halobacteriales, and Thermococcales. We review the available knowledge on control of DNA replication initiation in archaea

Replication Origins
Origin Recognition Proteins
C Sulfolobus acidocaldarius oriC1
Origin Binding and DNA Unwinding
Multiple Origins on the Chromosome
Recruitment of a Helicase
Regulation of DNA Replication Initiation
Cell Cycle Regulation in Haploid Archaea
Cell Cycle Regulation in Polyploid Archaea
Regulation of Initiation of Multiple Origins
Regulation of Replication of Multiple Chromosomal Elements
Alternative Mechanisms of Replication Initiation
Tools to Control Replication Initiation in Archaeal Cells
Spatial Organisation of Genome and Replication
Conclusions
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