title: HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment.
abstract: Telomeres are repetitive DNA structures that, together with the shelterin and the CST complex, protect the ends of chromosomes. Telomere shortening is mitigated in stem and cancer cells through the de novo addition of telomeric repeats by telomerase. Telomere elongation requires the delivery of the telomerase complex to telomeres through a not yet fully understood mechanism. Factors promoting telomerase-telomere interaction are expected to directly bind telomeres and physically interact with the telomerase complex. In search for such a factor we carried out a SILAC-based DNA-protein interaction screen and identified HMBOX1, hereafter referred to as homeobox telomere-binding protein 1 (HOT1). HOT1 directly and specifically binds double-stranded telomere repeats, with the in vivo association correlating with binding to actively processed telomeres. Depletion and overexpression experiments classify HOT1 as a positive regulator of telomere length. Furthermore, immunoprecipitation and cell fractionation analyses show that HOT1 associates with the active telomerase complex and promotes chromatin association of telomerase. Collectively, these findings suggest that HOT1 supports telomerase-dependent telomere elongation.
authors.affiliation: Medical Systems Biology, Faculty of Medicine Carl Gustav Carus, University Cancer Center, Dresden University of Technology, 01307 Dresden, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kappei
authors.forename: Falk
authors.initials: F
authors.lastname: Butter
authors.forename: Christian
authors.initials: C
authors.lastname: Benda
authors.forename: Marion
authors.initials: M
authors.lastname: Scheibe
authors.forename: Irena
authors.initials: I
authors.lastname: Draškovič
authors.forename: Michelle
authors.initials: M
authors.lastname: Stevense
authors.forename: Clara Lopes
authors.initials: CL
authors.lastname: Novo
authors.forename: Claire
authors.initials: C
authors.lastname: Basquin
authors.forename: Masatake
authors.initials: M
authors.lastname: Araki
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.forename: Dragomir Blazhev
authors.initials: DB
authors.lastname: Krastev
authors.forename: Ralf
authors.initials: R
authors.lastname: Kittler
authors.forename: Rolf
authors.initials: R
authors.lastname: Jessberger
authors.forename: J Arturo
authors.initials: JA
authors.lastname: Londoño-Vallejo
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Frank
authors.initials: F
authors.lastname: Buchholz
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid / Q000502:physiology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; C512050:HMBOX1 protein, human; D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; D034501:Telomere-Binding Proteins; D019098:Telomerase