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PMID:23746845

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Citation

Shi, T, Bunker, RD, Mattarocci, S, Ribeyre, C, Faty, M, Gut, H, Scrima, A, Rass, U, Rubin, SM, Shore, D and Thomä, NH (2013) Rif1 and Rif2 shape telomere function and architecture through multivalent Rap1 interactions. Cell 153:1340-53

Abstract

Yeast telomeres comprise irregular TG₁₋₃ DNA repeats bound by the general transcription factor Rap1. Rif1 and Rif2, along with Rap1, form the telosome, a protective cap that inhibits telomerase, counteracts SIR-mediated transcriptional silencing, and prevents inadvertent recognition of telomeres as DNA double-strand breaks. We provide a molecular, biochemical, and functional dissection of the protein backbone at the core of the yeast telosome. The X-ray structures of Rif1 and Rif2 bound to the Rap1 C-terminal domain and that of the Rif1 C terminus are presented. Both Rif1 and Rif2 have separable and independent Rap1-binding epitopes, allowing Rap1 binding over large distances (42-110 Å). We identify tetramerization (Rif1) and polymerization (Rif2) modules that, in conjunction with the long-range binding, give rise to a higher-order architecture that interlinks Rap1 units. This molecular Velcro relies on Rif1 and Rif2 to recruit and stabilize Rap1 on telomeric arrays and is required for telomere homeostasis in vivo.

Links

PubMed Online version:10.1016/j.cell.2013.05.007

Keywords

Amino Acid Sequence; Binding Sites; Chromosomes, Fungal/metabolism; Crystallography, X-Ray; Models, Molecular; Molecular Sequence Data; Protein Interaction Maps; Repressor Proteins/metabolism; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/metabolism; Sequence Alignment; Telomere/metabolism; Telomere-Binding Proteins/metabolism; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:RAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P29539

F

Seeded From UniProt

complete

YEAST:RAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q06208

F

Seeded From UniProt

complete

YEAST:RAP1

involved_in

GO:0000723: telomere maintenance

ECO:0005547: biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion

P

Seeded From UniProt

complete

YEAST:RAP1

located_in

GO:0070187: shelterin complex

ECO:0000353: physical interaction evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:RIF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11938

F

Seeded From UniProt

complete

YEAST:RIF1

involved_in

GO:0000723: telomere maintenance

ECO:0005547: biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion

P

Seeded From UniProt

complete

YEAST:RIF1

located_in

GO:0070187: shelterin complex

ECO:0000353: physical interaction evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:RIF2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11938

F

Seeded From UniProt

complete

YEAST:RIF2

involved_in

GO:0000723: telomere maintenance

ECO:0005547: biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion

P

Seeded From UniProt

complete

YEAST:RIF2

located_in

GO:0070187: shelterin complex

ECO:0000353: physical interaction evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:RAP1

part_of

GO:0070187: shelterin complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:RIF1

part_of

GO:0070187: shelterin complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11938

C

Seeded From UniProt

complete

YEAST:RIF2

part_of

GO:0070187: shelterin complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11938

C

Seeded From UniProt

complete

Notes

See also

References

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