title: TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends.
abstract: Mammalian chromosome ends are protected by a specialized nucleoprotein complex called telomeres. Both shelterin, a telomere-specific multi-protein complex, and higher order telomeric chromatin structures combine to stabilize the chromosome ends. Here, we showed that TRF2, a component of shelterin, binds to core histones to protect chromosome ends from inappropriate DNA damage response and loss of telomeric DNA. The N-terminal Gly/Arg-rich domain (GAR domain) of TRF2 directly binds to the globular domain of core histones. The conserved arginine residues in the GAR domain of TRF2 are required for this interaction. A TRF2 mutant with these arginine residues substituted by alanine lost the ability to protect telomeres and induced rapid telomere shortening caused by the cleavage of a loop structure of the telomeric chromatin. These findings showed a previously unnoticed interaction between the shelterin complex and nucleosomal histones to stabilize the chromosome ends.
authors: From the Department of Pathological Cell Biology and Medical Top Track Program, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan, the Department of Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan, and the Laboratory of Cell Biology and Genetics, The Rockefeller University, New York, New York 10065 akimitsukonishi@gunma-u.ac.jp.
authors: Akimitsu
authors: 0000-0002-3291-0821
authors: A
authors: Konishi
authors: the Department of Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan, and.
authors: Takashi
authors: T
authors: Izumi
authors: From the Department of Pathological Cell Biology and.
authors: Shigeomi
authors: S
authors: Shimizu
mesh_terms: D000818:Animals; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D000072417:Protein Domains; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis / Q000502:physiology*; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; C504753:TERF2 protein, human; C534796:TRF2 protein, mouse; D035341:Telomeric Repeat Binding Protein 2
keywords: DNA damage response; GAR domain; chromatin; chromosomes; core histone; histone; telomere