The Linear Hairpin Replicons of Borrelia burgdorferi

Kerri Kobryn

Dép. de Microbiologie et d'Infectiologie, Faculté de Médecine, Université de Sherbrooke,

3001, 12e Ave N., Sherbrooke, QC J1H 5N4, Canada

[email protected]

1 Introduction 118

2 Lyme Borreliosis 118

3 The Borrelia burgdorferi Genome 119

4 DNA Replication 120

4.1 Mode of Replication and Origins of Replication 120

4.2 Autonomous Replication and Plasmid Compatibility Functions 122

5 Telomere Resolution 124

5.1 In Vivo Demonstration of Telomere Resolution 124

5.2 The Telomere Resolvase (ResT) 125

5.3 Substrate Requirements for Telomere Resolution 127

5.4 Active Site Components of ResT 128

5.4.1 The Tyrosine Recombinase-Like Component of the Active Site 129

5.4.2 The Hairpin-Binding Module 130

5.5 Reaction Reversal by ResT 131

5.6 ResT's Relationship to Topoisomerases and Site-Specific Recombinases . . 132

5.7 Regulation of ResT Activity In Vivo 133

6 Perspectives 134

References 135

Abstract The genomes of the spirochetes of the genus Borrelia are unique among prokaryotes; all member species possess a linear chromosome as well as linear plasmids terminated by covalently closed DNA hairpins, or hairpin telomeres. The usual "end-replication problem" for linear replicons is overcome by the hairpin telomeres presenting to the cellular replication machinery an uninterrupted DNA chain. DNA replication initiates internally and proceeds bidirectionally. Replication through the hairpin turnaround at the telomeres produces replication intermediates that possess inverted repeat replicated telomere junctions, which act as the substrates for a specialized DNA breakage and reunion enzyme referred to as a telomere resolvase. The telomere resolvase converts each replicated telomere into two hairpin telomeres, thereby liberating linear daughter chromosomes from the replicated intermediates. The telomere resolution reaction has mechanistic similarities to those catalysed by type IB topoisomerases and tyrosine recombinases. Details of the replication and telomere resolution processes have been revealed by recent molecular biology and biochemical studies in Borrelia burgdorferi, the causative agent of Lyme disease.

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