Hairpin Telomere Resolvases

Abstract

Covalently closed hairpin ends, also known as hairpin telomeres, provide an unusual solution to the end replication problem. The hairpin telomeres are generated from replication intermediates by a process known as telomere resolution. This is a DNA breakage and reunion reaction promoted by hairpin telomere resolvases (also referred to as protelomerases) found in a limited number of phage and bacteria. The reaction promoted by these enzymes is a chemically isoenergetic two-step transesterification without a requirement for divalent metal ions or high-energy cofactors and uses an active site and mechanism similar to that for type IB topoisomerases and tyrosine recombinases. The small number of unrelated telomere resolvases characterized to date all contain a central, catalytic core domain with the active site, but in addition carry variable C-and N-terminal domains with different functions. Similarities and differences in the structure and function of the telomere resolvases are discussed. Of particular interest are the properties of the Borrelia telomere resolvases, which have been studied most extensively at the biochemical level and appear to play a role in shaping the unusual segmented genomes in these organisms and, perhaps, to play a role in recombinational events. HAIRPIN TELOMERE RESOLVASESHairpin telomere resolvases (also known as protelomerases) have emerged as a unique solution to the end replication problem (1, 2). These enzymes promote the formation of covalently closed hairpin ends on linear DNA molecules in some phage (3, 4, 5), bacterial plasmids and bacterial chromosomes (6,7,8,9). Telomere resolvases are mechanistically related to tyrosine recombinases and type IB topoisomerases and are also believed to play a role in the genome plasticity that characterizes Borrelia species. Fig. 1 shows the reaction pathway for replication of linear DNA molecules with covalently closed hairpin telomeres. Duplication of the DNA molecule results in replicated telomeres (rTel, also referred to as dimer junctions) that are recognized and processed in a DNA breakage and reunion reaction promoted by a hairpin telomere resolvase. The reaction products are covalently closed hairpin telomeres at both ends of linear monomeric DNA molecules. At this writing telomere resolvases have been purified from three phage and seven bacterial species: E. coli phage N15 (3), Klebsiella oxytoca phage φKO2, Yersinia enterocolitica phage PY54 (5), Agrobacterium tumefaciens (8), the Lyme spirochete Borrelia burgdorferi (6), the relapsing fever borreliae B. hermsii, B. parkeri, B. recurrentis, B. turicatae, and the avian spirochete B. anserina (7). The B. burgdorferi enzyme, ResT (Resolvase of Telomeres) has been the most extensively studied at the biochemical level (6,7,10,11,12,13,14,15,16,17,18,19,20,21,22,23) and is the primary focus of this review, with properties of the other enzymes noted (3,4,5,8,24). Structural studies of the Klebsiella phage φKO2 (25) and the Agrobacterium (26) resolvases have been reported and have she...

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