title: Localization-dependent and -independent roles of SLX4 in regulating telomeres.
abstract: SLX4, a scaffold for structure-specific DNA repair nucleases, is important for several types of DNA repair. Many repair proteins bind to sites of DNA damage, resulting in subnuclear "foci," but SLX4 forms foci in human cells even without DNA damage. Using several approaches, we show that most, but not all, SLX4 foci localize to telomeres in a range of human cell lines irrespective of the mechanisms used to maintain telomere length. The SLX1 Holliday-junction-processing enzyme is recruited to telomeres by SLX4, and SLX4, in turn, is recruited by a motif that binds to the shelterin subunit TRF2 directly. We also show that TRF2-dependent recruitment of SLX4 prevents telomere damage. Furthermore, SLX4 prevents telomere lengthening and fragility in a manner that appears to be independent of telomere association. These findings reveal that SLX4 plays multiple roles in regulating telomere homeostasis.
authors.affiliation: MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Jamie S J
authors.initials: JS
authors.lastname: Wilson
authors.forename: Agueda M
authors.initials: AM
authors.lastname: Tejera
authors.forename: Dennis
authors.initials: D
authors.lastname: Castor
authors.forename: Rachel
authors.initials: R
authors.lastname: Toth
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
authors.forename: John
authors.initials: J
authors.lastname: Rouse
mesh_terms: D045744:Cell Line, Tumor; D004260:DNA Repair; D006801:Humans; D045522:Recombinases / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*
chemical_list: D045522:Recombinases; C542319:SLX4 protein, human