title: RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity.
abstract: T loops and telomeric G-quadruplex (G4) DNA structures pose a potential threat to genome stability and must be dismantled to permit efficient telomere replication. Here we implicate the helicase RTEL1 in the removal of telomeric DNA secondary structures, which is essential for preventing telomere fragility and loss. In the absence of RTEL1, T loops are inappropriately resolved by the SLX4 nuclease complex, resulting in loss of the telomere as a circle. Depleting SLX4 or blocking DNA replication abolished telomere circles (TCs) and rescued telomere loss in RTEL1(-/-) cells but failed to suppress telomere fragility. Conversely, stabilization of telomeric G4-DNA or loss of BLM dramatically enhanced telomere fragility in RTEL1-deficient cells but had no impact on TC formation or telomere loss. We propose that RTEL1 performs two distinct functions at telomeres: it disassembles T loops and also counteracts telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.
authors.affiliation: DNA Damage Response laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms, UK.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Vannier
authors.forename: Visnja
authors.initials: V
authors.lastname: Pavicic-Kaltenbrunner
authors.forename: Mark I R
authors.initials: MI
authors.lastname: Petalcorin
authors.forename: Hao
authors.initials: H
authors.lastname: Ding
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Boulton
mesh_terms: D000818:Animals; D004265:DNA Helicases / Q000378:metabolism*; D004261:DNA Replication; D005347:Fibroblasts / Q000378:metabolism; D054856:G-Quadruplexes; D051379:Mice; D009690:Nucleic Acid Conformation; D045522:Recombinases / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
chemical_list: D045522:Recombinases; C543807:Slx4 protein, mouse; C527736:regulator of telomere length protein, mouse; D004265:DNA Helicases