An Interlocked Dimer of the Protelomerase TelK Distorts DNA Structure for the Formation of Hairpin Telomeres

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2007 Sep 25

PMID 17889664

Citations 21

Authors

Hideki Aihara

Wai Mun Huang

Tom Ellenberger

Affiliations

Soon will be listed here.

Abstract

The termini of linear chromosomes are protected by specialized DNA structures known as telomeres that also facilitate the complete replication of DNA ends. The simplest type of telomere is a covalently closed DNA hairpin structure found in linear chromosomes of prokaryotes and viruses. Bidirectional replication of a chromosome with hairpin telomeres produces a catenated circular dimer that is subsequently resolved into unit-length chromosomes by a dedicated DNA cleavage-rejoining enzyme known as a hairpin telomere resolvase (protelomerase). Here we report a crystal structure of the protelomerase TelK from Klebsiella oxytoca phage varphiKO2, in complex with the palindromic target DNA. The structure shows the TelK dimer destabilizes base pairing interactions to promote the refolding of cleaved DNA ends into two hairpin ends. We propose that the hairpinning reaction is made effectively irreversible by a unique protein-induced distortion of the DNA substrate that prevents religation of the cleaved DNA substrate.

Citing Articles

Design and characterization of hyperactive mutants of the Agrobacterium tumefaciens telomere resolvase, TelA.

Huang S, Abrametz K, McGrath S, Kobryn K PLoS One. 2024; 19(7):e0307590.

PMID: 39052566 PMC: 11271964. DOI: 10.1371/journal.pone.0307590.

Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain.

Semper C, Watanabe N, Karimullina E, Patel D, Di Leo R, Castellanos M Nucleic Acids Res. 2024; 52(14):8431-8442.

PMID: 38979576 PMC: 11317167. DOI: 10.1093/nar/gkae580.

The telomere resolvase, TelA, utilizes an underwound pre-cleavage intermediate to promote hairpin telomere formation.

Balouchi M, Huang S, McGrath S, Kobryn K PLoS One. 2023; 18(11):e0294732.

PMID: 38019799 PMC: 10686437. DOI: 10.1371/journal.pone.0294732.

The N-terminal domain of the Agrobacterium tumefaciens telomere resolvase, TelA, regulates its DNA cleavage and rejoining activities.

McGrath S, Huang S, Kobryn K J Biol Chem. 2022; 298(5):101951.

PMID: 35447111 PMC: 9111995. DOI: 10.1016/j.jbc.2022.101951.

Single stranded DNA annealing is a conserved activity of telomere resolvases.

McGrath S, Huang S, Kobryn K PLoS One. 2021; 16(2):e0246212.

PMID: 33539370 PMC: 7861564. DOI: 10.1371/journal.pone.0246212.

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