title: TRFH domain is critical for TRF1-mediated telomere stabilization.
abstract: The telomeres are nucleoprotein complexes essential for maintaining the genomic integrity of linear chromosomes. Six telomere localizing proteins form a complex named "shelterin/telosome" to cooperatively regulate telomere length and protect chromosomal ends from DNA damage and repair responses. Mouse embryonic stem (ES) cells lacking TRF1, a shelterin component, exhibit a high-incidence of broken or lost telomere FISH signals, supporting a critical role for TRF1 in telomere maintenance. We demonstrate that these abnormal telomere structures are not caused by the inability of TRF1-deficient cells to recruit TIN2 but are due to a specific role for TRF1 at telomeres. Furthermore, we provide evidence that the mTRF1 TRF homology (TRFH) domain is crucial for this abnormal telomere FISH phenotype. These novel findings suggest that the TRFH domain is crucial not only for dimerization of TRF1 and TIN2-telomere recruitment, but also telomere stabilization.
authors.affiliation: Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Okamoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
mesh_terms: D000818:Animals; D002645:Chickens; D043171:Chromosomal Instability; D004249:DNA Damage; D019281:Dimerization; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D010641:Phenotype; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; C499083:Tinf2 protein, mouse