title: Replication timing of human telomeres is chromosome arm-specific, influenced by subtelomeric structures and connected to nuclear localization.
abstract: The mechanisms governing telomere replication in humans are still poorly understood. To fill this gap, we investigated the timing of replication of single telomeres in human cells. Using in situ hybridization techniques, we have found that specific telomeres have preferential time windows for replication during the S-phase and that these intervals do not depend upon telomere length and are largely conserved between homologous chromosomes and between individuals, even in the presence of large subtelomeric segmental polymorphisms. Importantly, we show that one copy of the 3.3 kb macrosatellite repeat D4Z4, present in the subtelomeric region of the late replicating 4q35 telomere, is sufficient to confer both a more peripheral localization and a later-replicating property to a de novo formed telomere. Also, the presence of beta-satellite repeats next to a newly created telomere is sufficient to delay its replication timing. Remarkably, several native, non-D4Z4-associated, late-replicating telomeres show a preferential localization toward the nuclear periphery, while several early-replicating telomeres are associated with the inner nuclear volume. We propose that, in humans, chromosome arm-specific subtelomeric sequences may influence both the spatial distribution of telomeres in the nucleus and their replication timing.
authors.affiliation: Telomeres and Cancer Laboratory, Institut Curie, CNRS, UPMC University Paris 06, Paris, France.
authors.forename: Nausica
authors.initials: N
authors.lastname: Arnoult
authors.forename: Caroline
authors.initials: C
authors.lastname: Schluth-Bolard
authors.forename: Anne
authors.initials: A
authors.lastname: Letessier
authors.forename: Irena
authors.initials: I
authors.lastname: Drascovic
authors.forename: Rachida
authors.initials: R
authors.lastname: Bouarich-Bourimi
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
authors.forename: Sahn-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Amina
authors.initials: A
authors.lastname: Boussouar
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ottaviani
authors.forename: Frédérique
authors.initials: F
authors.lastname: Magdinier
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Arturo
authors.initials: A
authors.lastname: Londoño-Vallejo
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D004261:DNA Replication; D006801:Humans; D016196:S Phase; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000378:metabolism
chemical_list: D034501:Telomere-Binding Proteins; D019098:Telomerase