3owt › Citations

A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms.

Chen Y, Rai R, Zhou ZR, Kanoh J, Ribeyre C, Yang Y, Zheng H, Damay P, Wang F, Tsujii H, Hiraoka Y, Shore D, Hu HY, Chang S, Lei M
Nat Struct Mol Biol 18 213-21 (2011)
Related entries: 2l3n, 3k6g

Cited: 74 times
EuropePMC logo PMID: 21217703

Abstract

Repressor activator protein 1 (RAP1) is the most highly conserved telomere protein. It is involved in protecting chromosome ends in fission yeast and promoting gene silencing in Saccharomyces cerevisiae, whereas it represses homology-directed recombination at telomeres in mammals. To understand how RAP1 has such diverse functions at telomeres, we solved the crystal or solution structures of the RAP1 C-terminal (RCT) domains of RAP1 from multiple organisms in complex with their respective protein-binding partners. Our analysis establishes RAP1(RCT) as an evolutionarily conserved protein-protein interaction module. In mammalian and fission yeast cells, this module interacts with TRF2 and Taz1, respectively, targeting RAP1 to chromosome ends for telomere protection. In contrast, S. cerevisiae RAP1 uses its RCT domain to recruit Sir3 to telomeres to mediate gene silencing. Together, our results show that, depending on the organism, the evolutionarily conserved RAP1 RCT motif has diverse functional roles at telomeres.

Reviews - 3owt mentioned but not cited (1)

  1. Telomerase and telomere-associated proteins: structural insights into mechanism and evolution. Lewis KA, Wuttke DS. Structure 20 28-39 (2012)

Articles - 3owt mentioned but not cited (2)

  1. Modeling disordered protein interactions from biophysical principles. Peterson LX, Roy A, Christoffer C, Terashi G, Kihara D. PLoS Comput Biol 13 e1005485 (2017)
  2. A Two-Layer SVM Ensemble-Classifier to Predict Interface Residue Pairs of Protein Trimers. Lyu Y, Gong X. Molecules 25 E4353 (2020)


Reviews citing this publication (18)

  1. Shelterin-Mediated Telomere Protection. de Lange T. Annu Rev Genet 52 223-247 (2018)
  2. Complex interactions between the DNA-damage response and mammalian telomeres. Arnoult N, Karlseder J. Nat Struct Mol Biol 22 859-866 (2015)
  3. The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae. Gartenberg MR, Smith JS. Genetics 203 1563-1599 (2016)
  4. SIR proteins and the assembly of silent chromatin in budding yeast. Kueng S, Oppikofer M, Gasser SM. Annu Rev Genet 47 275-306 (2013)
  5. Epigenetics in Saccharomyces cerevisiae. Grunstein M, Gasser SM. Cold Spring Harb Perspect Biol 5 a017491 (2013)
  6. Structural biology of telomeres and telomerase. Smith EM, Pendlebury DF, Nandakumar J. Cell Mol Life Sci 77 61-79 (2020)
  7. The molecular biology of fruity and floral aromas in beer and other alcoholic beverages. Holt S, Miks MH, de Carvalho BT, Foulquié-Moreno MR, Thevelein JM. FEMS Microbiol Rev 43 193-222 (2019)
  8. SIR-nucleosome interactions: structure-function relationships in yeast silent chromatin. Oppikofer M, Kueng S, Gasser SM. Gene 527 10-25 (2013)
  9. The shelterin complex and hematopoiesis. Jones M, Bisht K, Savage SA, Nandakumar J, Keegan CE, Maillard I. J Clin Invest 126 1621-1629 (2016)
  10. Decoding telomere protein Rap1: Its telomeric and nontelomeric functions and potential implications in diabetic cardiomyopathy. Cai Y, Kandula V, Kosuru R, Ye X, Irwin MG, Xia Z. Cell Cycle 16 1765-1773 (2017)
  11. Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks. Fontana GA, Reinert JK, Thomä NH, Rass U. Microb Cell 5 327-343 (2018)
  12. Shelterin Complex at Telomeres: Implications in Ageing. Mir SM, Samavarchi Tehrani S, Goodarzi G, Jamalpoor Z, Asadi J, Khelghati N, Qujeq D, Maniati M. Clin Interv Aging 15 827-839 (2020)
  13. Multifunctionality of the Telomere-Capping Shelterin Complex Explained by Variations in Its Protein Composition. Ghilain C, Gilson E, Giraud-Panis MJ. Cells 10 1753 (2021)
  14. The regional sequestration of heterochromatin structural proteins is critical to form and maintain silent chromatin. Oh J, Yeom S, Park J, Lee JS. Epigenetics Chromatin 15 5 (2022)
  15. The role of telomere-binding modulators in pluripotent stem cells. Li F, Ge Y, Liu D, Songyang Z. Protein Cell 11 60-70 (2020)
  16. Keeping Balance Between Genetic Stability and Plasticity at the Telomere and Subtelomere of Trypanosoma brucei. Li B. Front Cell Dev Biol 9 699639 (2021)
  17. Regulation of Antigenic Variation by Trypanosoma brucei Telomere Proteins Depends on Their Unique DNA Binding Activities. Li B, Zhao Y. Pathogens 10 967 (2021)
  18. Close Ties between the Nuclear Envelope and Mammalian Telomeres: Give Me Shelter. Pennarun G, Picotto J, Bertrand P. Genes (Basel) 14 775 (2023)

Articles citing this publication (53)

  1. TRF2 recruits RTEL1 to telomeres in S phase to promote t-loop unwinding. Sarek G, Vannier JB, Panier S, Petrini JHJ, Boulton SJ. Mol Cell 57 622-635 (2015)
  2. TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions. Rai R, Chen Y, Lei M, Chang S. Nat Commun 7 10881 (2016)
  3. Clustered telomeres in phase-separated nuclear condensates engage mitotic DNA synthesis through BLM and RAD52. Min J, Wright WE, Shay JW. Genes Dev 33 814-827 (2019)
  4. Nontelomeric role for Rap1 in regulating metabolism and protecting against obesity. Yeung F, Ramírez CM, Mateos-Gomez PA, Pinzaru A, Ceccarini G, Kabir S, Fernández-Hernando C, Sfeir A. Cell Rep 3 1847-1856 (2013)
  5. Subtelomeric repetitive elements determine TERRA regulation by Rap1/Rif and Rap1/Sir complexes in yeast. Iglesias N, Redon S, Pfeiffer V, Dees M, Lingner J, Luke B. EMBO Rep 12 587-593 (2011)
  6. Rif1 and Rif2 shape telomere function and architecture through multivalent Rap1 interactions. Shi T, Bunker RD, Mattarocci S, Ribeyre C, Faty M, Gut H, Scrima A, Rass U, Rubin SM, Shore D, Thomä NH. Cell 153 1340-1353 (2013)
  7. Human Rap1 interacts directly with telomeric DNA and regulates TRF2 localization at the telomere. Arat NÖ, Griffith JD. J Biol Chem 287 41583-41594 (2012)
  8. The molecular topography of silenced chromatin in Saccharomyces cerevisiae. Thurtle DM, Rine J. Genes Dev 28 245-258 (2014)
  9. Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex. Hu C, Rai R, Huang C, Broton C, Long J, Xu Y, Xue J, Lei M, Chang S, Chen Y. Cell Res 27 1485-1502 (2017)
  10. Human Rap1 modulates TRF2 attraction to telomeric DNA. Janoušková E, Nečasová I, Pavloušková J, Zimmermann M, Hluchý M, Marini V, Nováková M, Hofr C. Nucleic Acids Res 43 2691-2700 (2015)
  11. Reconstitution of human shelterin complexes reveals unexpected stoichiometry and dual pathways to enhance telomerase processivity. Lim CJ, Zaug AJ, Kim HJ, Cech TR. Nat Commun 8 1075 (2017)
  12. Structural basis for the role of the Sir3 AAA+ domain in silencing: interaction with Sir4 and unmethylated histone H3K79. Ehrentraut S, Hassler M, Oppikofer M, Kueng S, Weber JM, Mueller JW, Gasser SM, Ladurner AG, Ehrenhofer-Murray AE. Genes Dev 25 1835-1846 (2011)
  13. End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1. Lescasse R, Pobiega S, Callebaut I, Marcand S. EMBO J 32 805-815 (2013)
  14. Tpz1 controls a telomerase-nonextendible telomeric state and coordinates switching to an extendible state via Ccq1. Jun HI, Liu J, Jeong H, Kim JK, Qiao F. Genes Dev 27 1917-1931 (2013)
  15. Fission yeast shelterin regulates DNA polymerases and Rad3(ATR) kinase to limit telomere extension. Chang YT, Moser BA, Nakamura TM. PLoS Genet 9 e1003936 (2013)
  16. Identification of the functional domains of the telomere protein Rap1 in Schizosaccharomyces pombe. Fujita I, Tanaka M, Kanoh J. PLoS One 7 e49151 (2012)
  17. Assessing the performance of MM/PBSA and MM/GBSA methods. 9. Prediction reliability of binding affinities and binding poses for protein-peptide complexes. Weng G, Wang E, Chen F, Sun H, Wang Z, Hou T. Phys Chem Chem Phys 21 10135-10145 (2019)
  18. Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy. Khattar E, Maung KZY, Chew CL, Ghosh A, Mok MMH, Lee P, Zhang J, Chor WHJ, Cildir G, Wang CQ, Mohd-Ismail NK, Chin DWL, Lee SC, Yang H, Shin YJ, Nam DH, Chen L, Kumar AP, Deng LW, Ikawa M, Gunaratne J, Osato M, Tergaonkar V. Nat Commun 10 5349 (2019)
  19. Endothelial senescence is induced by phosphorylation and nuclear export of telomeric repeat binding factor 2-interacting protein. Kotla S, Vu HT, Ko KA, Wang Y, Imanishi M, Heo KS, Fujii Y, Thomas TN, Gi YJ, Mazhar H, Paez-Mayorga J, Shin JH, Tao Y, Giancursio CJ, Medina JL, Taunton J, Lusis AJ, Cooke JP, Fujiwara K, Le NT, Abe JI. JCI Insight 4 124867 (2019)
  20. The orientation of the C-terminal domain of the Saccharomyces cerevisiae Rap1 protein is determined by its binding to DNA. Matot B, Le Bihan YV, Lescasse R, Pérez J, Miron S, David G, Castaing B, Weber P, Raynal B, Zinn-Justin S, Gasparini S, Le Du MH. Nucleic Acids Res 40 3197-3207 (2012)
  21. A higher-order entity formed by the flexible assembly of RAP1 with TRF2. Gaullier G, Miron S, Pisano S, Buisson R, Le Bihan YV, Tellier-Lebègue C, Messaoud W, Roblin P, Guimarães BG, Thai R, Giraud-Panis MJ, Gilson E, Le Du MH. Nucleic Acids Res 44 1962-1976 (2016)
  22. Fission yeast Cactin restricts telomere transcription and elongation by controlling Rap1 levels. Lorenzi LE, Bah A, Wischnewski H, Shchepachev V, Soneson C, Santagostino M, Azzalin CM. EMBO J 34 115-129 (2015)
  23. Natural Selection Footprints Among African Chicken Breeds and Village Ecotypes. Elbeltagy AR, Bertolini F, Fleming DS, Van Goor A, Ashwell CM, Schmidt CJ, Kugonza DR, Lamont SJ, Rothschild MF. Front Genet 10 376 (2019)
  24. Minishelterins separate telomere length regulation and end protection in fission yeast. Pan L, Hildebrand K, Stutz C, Thomä N, Baumann P. Genes Dev 29 1164-1174 (2015)
  25. Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly. Cicconi A, Rai R, Xiong X, Broton C, Al-Hiyasat A, Hu C, Dong S, Sun W, Garbarino J, Bindra RS, Schildkraut C, Chen Y, Chang S. Nat Commun 11 5861 (2020)
  26. PRL-3 promotes telomere deprotection and chromosomal instability. Lian S, Meng L, Yang Y, Ma T, Xing X, Feng Q, Song Q, Liu C, Tian Z, Qu L, Shou C. Nucleic Acids Res 45 6546-6571 (2017)
  27. Zscan4 interacts directly with human Rap1 in cancer cells regardless of telomerase status. Lee K, Gollahon LS. Cancer Biol Ther 15 1094-1105 (2014)
  28. Structure of the fission yeast S. pombe telomeric Tpz1-Poz1-Rap1 complex. Xue J, Chen H, Wu J, Takeuchi M, Inoue H, Liu Y, Sun H, Chen Y, Kanoh J, Lei M. Cell Res 27 1503-1520 (2017)
  29. Trypanosoma brucei RAP1 Has Essential Functional Domains That Are Required for Different Protein Interactions. Afrin M, Kishmiri H, Sandhu R, Rabbani MAG, Li B. mSphere 5 e00027-20 (2020)
  30. Increase in lamin B1 promotes telomere instability by disrupting the shelterin complex in human cells. Pennarun G, Picotto J, Etourneaud L, Redavid AR, Certain A, Gauthier LR, Fontanilla-Ramirez P, Busso D, Chabance-Okumura C, Thézé B, Boussin FD, Bertrand P. Nucleic Acids Res 49 9886-9905 (2021)
  31. The evolution of metazoan shelterin. Myler LR, Kinzig CG, Sasi NK, Zakusilo G, Cai SW, de Lange T. Genes Dev 35 1625-1641 (2021)
  32. Endothelial senescence-associated secretory phenotype (SASP) is regulated by Makorin-1 ubiquitin E3 ligase. Kotla S, Le NT, Vu HT, Ko KA, Gi YJ, Thomas TN, Giancursio C, Lusis AJ, Cooke JP, Fujiwara K, Abe JI. Metabolism 100 153962 (2019)
  33. The Replisome Mediates A-NHEJ Repair of Telomeres Lacking POT1-TPP1 Independently of MRN Function. Rai R, Gu P, Broton C, Kumar-Sinha C, Chen Y, Chang S. Cell Rep 29 3708-3725.e5 (2019)
  34. Complete sequences of Schizosaccharomyces pombe subtelomeres reveal multiple patterns of genome variation. Oizumi Y, Kaji T, Tashiro S, Takeshita Y, Date Y, Kanoh J. Nat Commun 12 611 (2021)
  35. Insights into POT1 structural dynamics revealed by cryo-EM. Smith EW, Lattmann S, Liu ZB, Ahsan B, Rhodes D. PLoS One 17 e0264073 (2022)
  36. Purification and characterization of the fission yeast telomere clustering factors, Bqt1 and Bqt2. Ichikawa Y, Kagawa W, Saito K, Chikashige Y, Haraguchi T, Hiraoka Y, Kurumizaka H. Protein Expr Purif 88 207-213 (2013)
  37. Shelterin is a dimeric complex with extensive structural heterogeneity. Zinder JC, Olinares PDB, Svetlov V, Bush MW, Nudler E, Chait BT, Walz T, de Lange T. Proc Natl Acad Sci U S A 119 e2201662119 (2022)
  38. Telomere-binding proteins Taz1 and Rap1 regulate DSB repair and suppress gross chromosomal rearrangements in fission yeast. Irie H, Yamamoto I, Tarumoto Y, Tashiro S, Runge KW, Ishikawa F. PLoS Genet 15 e1008335 (2019)
  39. A Taz1- and Microtubule-Dependent Regulatory Relationship between Telomere and Centromere Positions in Bouquet Formation Secures Proper Meiotic Divisions. Katsumata K, Hirayasu A, Miyoshi J, Nishi E, Ichikawa K, Tateho K, Wakuda A, Matsuhara H, Yamamoto A. PLoS Genet 12 e1006304 (2016)
  40. Hypothesis: Paralog Formation from Progenitor Proteins and Paralog Mutagenesis Spur the Rapid Evolution of Telomere Binding Proteins. Lustig AJ. Front Genet 7 10 (2016)
  41. Identification of a transcriptional activation domain in yeast repressor activator protein 1 (Rap1) using an altered DNA-binding specificity variant. Johnson AN, Weil PA. J Biol Chem 292 5705-5723 (2017)
  42. Inhibition of MRN activity by a telomere protein motif. Khayat F, Cannavo E, Alshmery M, Foster WR, Chahwan C, Maddalena M, Smith C, Oliver AW, Watson AT, Carr AM, Cejka P, Bianchi A. Nat Commun 12 3856 (2021)
  43. Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states. Barry RM, Sacco O, Mameri A, Stojaspal M, Kartsonis W, Shah P, De Ioannes P, Hofr C, Côté J, Sfeir A. Genes Dev 36 313-330 (2022)
  44. TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress. Higa M, Matsuda Y, Fujii J, Sugimoto N, Yoshida K, Fujita M. Nucleic Acids Res 49 12234-12251 (2021)
  45. Variants of the Sir4 Coiled-Coil Domain Improve Binding to Sir3 for Heterochromatin Formation in Saccharomyces cerevisiae. Samel A, Rudner A, Ehrenhofer-Murray AE. G3 (Bethesda) 7 1117-1126 (2017)
  46. Casein kinase 2 regulates telomere protein complex formation through Rap1 phosphorylation. Inoue H, Horiguchi M, Ono K, Kanoh J. Nucleic Acids Res 47 6871-6884 (2019)
  47. Aberrant expression and localization of the RAP1 shelterin protein contribute to age-related phenotypes. Stock AJ, McDevitt RA, Puligilla C, Wang Y, Zhang Y, Wang K, Sun C, Becker KG, Lehrmann E, Wood WH, Gong Y, Aqdas M, Sung MH, Hoffmann V, Liu C, Gorospe M, Harrington L, Ferrucci L, Liu Y. PLoS Genet 18 e1010506 (2022)
  48. Phytochemicals, Antioxidant Attributes and Larvicidal Activity of Mercurialis annua L. (Euphorbiaceae) Leaf Extracts against Tribolium confusum (Du Val) Larvae (Coleoptera; Tenebrionidae). Ben Nasr R, Baudelaire ED, Dicko A, El Ferchichi Ouarda H. Biology (Basel) 10 344 (2021)
  49. Rap1 prevents fusions between long telomeres in fission yeast. Pan L, Tormey D, Bobon N, Baumann P. EMBO J 41 e110458 (2022)
  50. Structural insights into Pot1-ssDNA, Pot1-Tpz1 and Tpz1-Ccq1 Interactions within fission yeast shelterin complex. Sun H, Wu Z, Zhou Y, Lu Y, Lu H, Chen H, Shi S, Zeng Z, Wu J, Lei M. PLoS Genet 18 e1010308 (2022)
  51. TIN2 is an architectural protein that facilitates TRF2-mediated trans- and cis-interactions on telomeric DNA. Kaur P, Barnes R, Pan H, Detwiler AC, Liu M, Mahn C, Hall J, Messenger Z, You C, Piehler J, Smart RC, Riehn R, Opresko PL, Wang H. Nucleic Acids Res 49 13000-13018 (2021)
  52. The cooperative assembly of shelterin bridge provides a kinetic gateway that controls telomere length homeostasis. Liu J, Hu X, Bao K, Kim JK, Zhang C, Jia S, Qiao F. Nucleic Acids Res 49 8110-8119 (2021)
  53. Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2B and RAP1. Rai R, Biju K, Sun W, Sodeinde T, Al-Hiyasat A, Morgan J, Ye X, Li X, Chen Y, Chang S. Nat Commun 14 2144 (2023)


Quick links