title: A higher-order entity formed by the flexible assembly of RAP1 with TRF2.
abstract: Telomere integrity is essential to maintain genome stability, and telomeric dysfunctions are associated with cancer and aging pathologies. In human, the shelterin complex binds TTAGGG DNA repeats and provides capping to chromosome ends. Within shelterin, RAP1 is recruited through its interaction with TRF2, and TRF2 is required for telomere protection through a network of nucleic acid and protein interactions. RAP1 is one of the most conserved shelterin proteins although one unresolved question is how its interaction may influence TRF2 properties and regulate its capacity to bind multiple proteins. Through a combination of biochemical, biophysical and structural approaches, we unveiled a unique mode of assembly between RAP1 and TRF2. The complete interaction scheme between the full-length proteins involves a complex biphasic interaction of RAP1 that directly affects the binding properties of the assembly. These results reveal how a non-DNA binding protein can influence the properties of a DNA-binding partner by mutual conformational adjustments.
authors.affiliation: Department of Biochemistry, Biophysics and Structural Biology, Institute for Integrative Biology of the Cell (I2BC), CEA, UMR 9198 CNRS, Université Paris-Sud, Batiment 144, CEA Saclay, Gif-sur-Yvette, F-91191, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gaullier
authors.affiliation: Department of Biochemistry, Biophysics and Structural Biology, Institute for Integrative Biology of the Cell (I2BC), CEA, UMR 9198 CNRS, Université Paris-Sud, Batiment 144, CEA Saclay, Gif-sur-Yvette, F-91191, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Miron
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN); CNRS UMR7284/INSERM U1081; Faculty of Medicine; Nice, 06107, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pisano
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN); CNRS UMR7284/INSERM U1081; Faculty of Medicine; Nice, 06107, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Buisson
authors.affiliation: Department of Biochemistry, Biophysics and Structural Biology, Institute for Integrative Biology of the Cell (I2BC), CEA, UMR 9198 CNRS, Université Paris-Sud, Batiment 144, CEA Saclay, Gif-sur-Yvette, F-91191, France.
authors.forename: Yann-Vaï
authors.initials: YV
authors.lastname: Le Bihan
authors.affiliation: Department of Biochemistry, Biophysics and Structural Biology, Institute for Integrative Biology of the Cell (I2BC), CEA, UMR 9198 CNRS, Université Paris-Sud, Batiment 144, CEA Saclay, Gif-sur-Yvette, F-91191, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Tellier-Lebègue
authors.affiliation: Department of Biochemistry, Biophysics and Structural Biology, Institute for Integrative Biology of the Cell (I2BC), CEA, UMR 9198 CNRS, Université Paris-Sud, Batiment 144, CEA Saclay, Gif-sur-Yvette, F-91191, France.
authors.forename: Wala
authors.initials: W
authors.lastname: Messaoud
authors.affiliation: Synchrotron SOLEIL, L'Orme des Merisiers, Saint-Aubin BP 48, 91192 GIF-SUR-YVETTE Cedex, France Institut National de la Recherche Agronomique, Unité Biopolymères, Interactions, Assemblages, 44316 Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roblin
authors.affiliation: Synchrotron SOLEIL, L'Orme des Merisiers, Saint-Aubin BP 48, 91192 GIF-SUR-YVETTE Cedex, France.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Guimarães
authors.affiliation: CEA, iBiTecS, F-91191 Gif-sur-Yvette, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Thai
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN); CNRS UMR7284/INSERM U1081; Faculty of Medicine; Nice, 06107, France.
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN); CNRS UMR7284/INSERM U1081; Faculty of Medicine; Nice, 06107, France Department of Genetics, CHU; Nice, 06107, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.affiliation: Department of Biochemistry, Biophysics and Structural Biology, Institute for Integrative Biology of the Cell (I2BC), CEA, UMR 9198 CNRS, Université Paris-Sud, Batiment 144, CEA Saclay, Gif-sur-Yvette, F-91191, France marie-helene.ledu@cea.fr.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Le Du
mesh_terms: D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D046912:Multiprotein Complexes; D011485:Protein Binding; D000089804:Shelterin Complex; D016615:Telomere / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D000089804:Shelterin Complex; C504753:TERF2 protein, human; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2