The DOI matches its Crossref record; 36 of the 38 references it cites were found in a registry or an index.
A Protein-Counting Mechanism for Telomere Length Regulation in Yeast
Open accessAbstract
In the yeast Saccharomyces cerevisiae , telomere elongation is negatively regulated by the telomere repeat-binding protein Rap1p, such that a narrow length distribution of telomere repeat tracts is observed. This length regulation was shown to function independently of the orientation of the telomere repeats. The number of repeats at an individual telomere was reduced when hybrid proteins containing the Rap1p carboxyl terminus were targeted there by a heterologous DNA-binding domain. The extent of this telomere tract shortening was proportional to the number of targeted molecules, consistent with a feedback mechanism of telomere length regulation that can discriminate the precise number of Rap1p molecules bound to the chromosome end.
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“However, a strong common theme that has emerged is the likely involvement of a protein-counting mechanism in both systems (31, 44).”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [31]
Citations
Cites
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
WATSON, J. D. (1972) · Nature New Biology · doi:10.1038/newbio239197a0 · Cited by 1,632
Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription
Gottschling, D. E., Aparicio, O. M., Billington, B. L., & Zakian, V. A. (1990) · Cell · doi:10.1016/0092-8674(90)90141-z · Cited by 1,325
Greider, C. W. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.002005 · Cited by 1,032
Telomeres: Beginning to Understand the End
Zakian, V. A. (1995) · Science · doi:10.1126/science.270.5242.1601 · Cited by 859
TLC1 : Template RNA Component of Saccharomyces cerevisiae Telomerase
Singer, M. S., & Gottschling, D. E. (1994) · Science · doi:10.1126/science.7545955 · Cited by 736
Chong, L., van Steensel, B., Broccoli, D., Erdjument‐Bromage, H., Hanish, J., Tempst, P., & de Lange, T. (1995) · Science · doi:10.1126/science.270.5242.1663 · Cited by 714
Cdc13p: A Single-Strand Telomeric DNA-Binding Protein with a Dual Role in Yeast Telomere Maintenance
Nugent, C. I., Hughes, T., Lue, N. F., & Lundblad, V. (1996) · Science · doi:10.1126/science.274.5285.249 · Cited by 606
Moretti, P. M., Freeman, K., Coodly, L. R., & Shore, D. (1994) · Genes & Development · doi:10.1101/gad.8.19.2257 · Cited by 547
Self-citationYUDKIN, J. (1972) · Nature · doi:10.1038/239197a0 · Cited by 545
Research works printed but not linked: 11
- ibid. 51, 887 (1987);
- Harley C. B., Telomeres,, Blackburn E., Greider C., Eds. (Cold Spring Harbor Press, Plainview, NY, 1995247-263).
- Lustig A. J. and , Petes T. D., ibid. 83, 1398 (1986).
- Krauskopf A. and , Blackburn E. H., ibid. 383, 354 (1996);
- Buck S. thesis Columbia University (1996).
- Kyrion G., Boakye K. A., Lustig A. J., Mol. Cell. Biol. 12, 5159 (1992).
- Overexpression of the COOH-terminal half of Rap1p from a high-copy number plasmid was reported to cause telomere lengthening (5) [C. F. J. Hardy thesis Columbia University (1991)]. In our experiments the Gbd/Rap1 hybrid was expressed on a centromere plasmid by means of the RAP1 promoter which most likely explains its lack of effect on telomere length in the absence of UAS G sites.
- Chien C.-T., Buck S., Sternglanz R., Shore D., ibid.531.
- Grandin N. , Reed S. I. , Charbonneau M., Genes Dev., in press.
- Wotton D. and , Shore D., ibid., in press.
- van Steensel B. de Lange T. Nature in press.
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Items 101–200 of 522
O’Donnell, S., Yue, J., Saada, O. A., Agier, N., Caradec, C., Cokelaer, T., Chiara, M. D., Delmas, S., Dutreux, F., Fournier, T., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01459-y · Cited by 128
Rif1 and Rif2 Inhibit Localization of Tel1 to DNA Ends
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“The Rap1-Rif1-Rif2 complex creates a negative feedback loop that regulates telomere length (Levy and Blackburn, 2004; Marcand et al., 1997; Wotton and Shore, 1997), but the molecular details of this feedback mechanism are not fully understood.”
BackgroundDelivery of Yeast Telomerase to a DNA Break Depends on the Recruitment Functions of Cdc13 and Est1
Bianchi, A., Negrini, S., & Shore, D. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.09.009 · Cited by 131
Self-citationThe Budding Yeast NucleusPreprint
Taddei, A., Schober, H., & Gasser, S. M. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000612 · Cited by 131
“The bifunctional role of Sir4 as a mediator of repression and an anchor for silent chromatin provides a mechanism for the self-organization of repressive compartments.”
BackgroundInfluentialCounting of Rif1p and Rif2p on Saccharomyces cerevisiae Telomeres Regulates Telomere Length
Levy, D. L., & Blackburn, E. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10857-10867.2004 · Cited by 131
“similar to that reported with tethered Rap1p C termini (32)”
BackgroundResultShakirov, E. V., Surovtseva, Y. V., Osbun, N. C., & Shippen, D. E. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.17.7725-7733.2005 · Cited by 130
“Alternatively, as has been shown for the human P1( OB) protein (29), this truncated Arabidopsis polypeptide may remain associated with telomeres via protein-protein interactions, directly influencing the telomere-counting mechanism proposed to regulate the length of the telomere tract (31, 43).”
BackgroundMechanisms of silencing in Saccharomyces cerevisiae
Lustig, A. J. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80146-9 · Cited by 129
Li, S., Makovets, S., Matsuguchi, T., Blethrow, J. D., Shokat, K. M., & Blackburn, E. H. (2009) · Cell · doi:10.1016/j.cell.2008.11.027 · Cited by 128
“In yeast strains lacking the Rap1 C terminus, Rif1, or Rif2, telomere length homeostasis is disabled and long telomeres ensue (Levy and Blackburn, 2004; Marcand et al., 1997).”
RAP1 Protects from Obesity through Its Extratelomeric Role Regulating Gene Expression
Martínez, P., Goméz-López, G., Garcı́a, F., Mercken, E. M., Mitchell, S. J., Flores, J. M., de Cabo, R., & Blasco, M. A. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.05.030 · Cited by 129
“…scRap1 is the major binding activity at telomeres where it controls telomere length and the establishment of subtelomeric silencing through recruitment of the Sir proteins (Carmen et al., 2002; Hecht et al., 1995; Imai et al., 2000; Kyrion et al., 1993; Marcand et al., 1997; Tanny et al., 1999).”
BackgroundGetting to the end: telomerase access in yeast and humans
Vega, L. R., Mateyak, M. K., & Zakian, V. A. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1256 · Cited by 129
“The inclusion of Rap1-binding sites that are internal to a telomere 'seed' results in the addition of fewer TG 1–3 repeats to the end bearing these sites, which indicates that Rap1 acts in cis to negatively regulate telomere lengt”
BackgroundTelomerase-dependent repeat divergence at the 3' ends of yeast telomeres
Förstemann, K. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.14.2690 · Cited by 118
Doshi, J. M., Tian, D., & Xing, C. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060968r · Cited by 119
Telomerase and chromosome end maintenance
Lingner, J., & Cech, T. R. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80145-7 · Cited by 120
Multiple Interactions in Sir Protein Recruitment by Rap1p at Silencers and Telomeres in Yeast
Moretti, P., & Shore, D. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.23.8082-8094.2001 · Cited by 118
“At telomeres, multiple Rap1p binding sites are found within the terminal TG1–3 repeats (16, 33), where the Rap1 protein is involved in regulation of both telomere structure and telomeric silencing (8, 27, 28, 32, 41, 47).”
BackgroundSelf-citationTelomere and Telomerase Biology
Giardini, M. A., Segatto, M., da Silva, M. S., Nunes, V. S., & Cano, M. I. N. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-397898-1.00001-3 · Cited by 131
MRE11–RAD50–NBS1 and ATM function as co-mediators of TRF1 in telomere length control
Wu, Y., Xiao, S., & Zhu, X. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1286 · Cited by 119
“The functional orthologs of TRF1 in the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe are Rap1 and Taz1, respectivel”
BackgroundDistinct roles for yeast Stn1 in telomere capping and telomerase inhibition
Puglisi, A., Bianchi, A., Lemmens, L., Damay, P., & Shore, D. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.158 · Cited by 115
“Mutations in RIF1 and RIF2, part of the so-called ‘protein-counting’ mechanism (Marcand et al, 1997, 1999), lead to telomere over-elongation, whereas mutations in components of the MRX complex (Mre11, Rad50 or Xrs2) or Tel1 (the yeast ATM homologue) have been shown to result in short, but stable…”
BackgroundSelf-citationRAP, RAP, open up! New wrinkles for RAP1 in yeast
Morse, R. H. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(99)01936-8 · Cited by 116
Chromosome End Maintenance by Telomerase
Osterhage, J. L., & Friedman, K. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.r900011200 · Cited by 119
How Cells Know the Size of Their Organelles
Chan, Y.-H. M., & Marshall, W. F. (2012) · Science · doi:10.1126/science.1223539 · Cited by 113
Telomere-bound TRF1 and TRF2 stall the replication fork at telomeric repeats
Ohki, R. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh309 · Cited by 114
“This ‘protein-counting model’ was originally proposed in yeast ( 6 ).”
BackgroundMultiple pathways inhibit NHEJ at telomeresPreprint
Marcand, S., Pardo, B., Gratias, A., Cahun, S., & Callebaut, I. (2008) · Genes & Development · doi:10.1101/gad.455108 · Cited by 108
“This hybrid establishes transcriptional silencing and participates in the negative feedback loop on telomere elongation when targeted to the internal edge of a telomere (Buck and Shore 1995; Marcand et al. 1997).”
BackgroundSelf-citationRif1 and Rif2 Shape Telomere Function and Architecture through Multivalent Rap1 Interactions
Shi, T., Bunker, R. D., Mattarocci, S., Ribeyre, C., Faty, M., Gut, H., Scrima, A., Rass, U., Rubin, S. M., Shore, D., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.007 · Cited by 110
Self-citationTelomeric Protein Pin2/TRF1 as an Important ATM Target in Response to Double Strand DNA Breaks
Kishi, S., Zhou, X. Z., Ziv, Y., Khoo, C., HILL, D. E., Shiloh, Y., & Lu, K. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011534200 · Cited by 116
Cdc13 Cooperates with the Yeast Ku Proteins and Stn1 To Regulate Telomerase Recruitment
Grandin, N., Damon‐Soubeyrand, C., & Charbonneau, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8397-8408.2000 · Cited by 110
“It has been suggested that the Rap1-dependent telomere lengthsensing mechanism (36) might be mediated by a balance between opposing effects of Rif1 or Rif2 and those of Sir3 or Sir4 (59).”
BackgroundMechanisms and regulation of DNA end resection
Longhese, M. P., Bonetti, D., Manfrini, N., & Clerici, M. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.165 · Cited by 117
“…by the Rap1 protein that, together with its interactors Rif1 and Rif2, binds telomeric double-stranded DNA repeats and inhibits both telomerase-dependent telomere elongation (Hardy et al, 1992; Marcand et al, 1997; Levy and Blackburn, 2004) and telomere fusions by NHEJ (Marcand et al, 2008).”
BackgroundThe Function of DNA Polymerase α at Telomeric G Tails Is Important for Telomere Homeostasis
Martin, A. A., Dionne, I., Wellinger, R. J., & Holm, C. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.3.786-796.2000 · Cited by 109
“For example, the partial loss of duplex DNA at the telomeres in cdc17/pol1 mutants may create an unfavorable environment for the binding of the telomere-binding Rap1 protein; Rap1p requires duplex DNA for binding (6, 12, 36) and is central in the mechanism of telomere length control (39).”
BackgroundEpigenetics in Saccharomyces cerevisiaePreprint
Grunstein, M. R., & Gasser, S. M. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a017491 · Cited by 112
“This array of Rap1 binding sites forms a nonnucleosomal cap on the chromosomal end, and plays a critical role in telomere length maintenance (Kyrion et al. 1992; Marcand et al. 1997).”
BackgroundAksenova, A. Y., & Mirkin, S. M. (2019) · Genes · doi:10.3390/genes10020118 · Cited by 114
“One perplexing question is what mechanisms are responsible for species-specific telomere length homeostasis? Current models include the protein-counting mechanism and/or the replication fork model [191,192].”
BackgroundShelterin-Like Proteins and Yku Inhibit Nucleolytic Processing of Saccharomyces cerevisiae Telomeres
Bonetti, D., Clerici, M., Anbalagan, S., Martina, M., Lucchini, G., & Longhese, M. P. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000966 · Cited by 106
“and telomerase-dependent telomere elongation [22,23].”
Medek, A., Hajduk, P. J., Mack, J. C., & Fesik, S. W. (2000) · Journal of the American Chemical Society · doi:10.1021/ja993921m · Cited by 104
Sequence-specific DNA Recognition by the Myb-like Domain of Plant Telomeric Protein RTBP1
Yu, E. Y., Kim, S. E., Kim, J. H., Ko, J., Cho, M. H., & Chung, I. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003250200 · Cited by 103
Telomere Length Dynamics in Telomerase-Positive Immortal Human Cell Populations
Bryan, T. M., Englezou, A., Dunham, M. A., & Reddel, R. R. (1998) · Experimental Cell Research · doi:10.1006/excr.1997.3907 · Cited by 105
Early Replication of Short Telomeres in Budding Yeast
Bianchi, A., & Shore, D. (2007) · Cell · doi:10.1016/j.cell.2007.01.041 · Cited by 106
Self-citationThe Length of the Shortest Telomere as the Major Determinant of the Onset of Replicative Senescence
Xu, Z., Duc, K. D., Holcman, D., & Teixeira, M. T. (2013) · Genetics · doi:10.1534/genetics.113.152322 · Cited by 107
“10 cerevisiae, this mechanism rests on the coating of telomeric repeats by the protein Rap1, 11 which, through its interaction with the Rap1-Interacting Factors Rif1 and Rif2, inhibits 12 telomerase elongation (Hardy et al. 1992; Marcand et al. 1997; Wotton and Shore 1997).”
BackgroundInfluentialIglesias, N., Redon, S., Pfeiffer, V., Dees, M., Lingner, J., & Luke, B. (2011) · EMBO Reports · doi:10.1038/embor.2011.73 · Cited by 102
“Rap1 is essential for telomerelength regulation, chromosome-end protection and silencing of subtelomeric inserted reporter genes (Kyrion et al, 1993; Shore, 1994; Marcand et al, 1997; Pardo & Marcand, 2005).”
BackgroundBiochemical aspects of telomerase function
Harrington, L. A. (2003) · Cancer Letters · doi:10.1016/s0304-3835(02)00701-2 · Cited by 101
“Telomerase elongation in vivo is a complex and dynamic process that is negatively regulated by double-stranded telomere-binding proteins, including RAP1 in budding yeast [45–51], and TRF1 in humans [52,53] (reviewed in Ref.”
BackgroundInteraction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions
Corda, Y., Schramke, V., Longhese, M. P., Smokvina, T., Paciotti, V., Brevet, V., Gilson, É., & Géli, V. (1999) · Nature Genetics · doi:10.1038/5991 · Cited by 99
“, a speculative model is that MEC3 and/or SET1 participates in the coupling of DNA replication and/or telomerase activity to proteins that sense telomere lengt”
Telomeres and telomerasePreprint
Blasco, M. A., Gasser, S. M., & Lingner, J. (1999) · Genes & Development · doi:10.1101/gad.13.18.2353 · Cited by 99
“…(University of Geneva, Switzerland) and Eric Gilson (Ecole Normale Supérieure, France) has shown that the telomerase-dependent extension of the TG-rich strand in yeast is regulated by a negative feedback mechanism that monitors the length of the doublestranded TG-rich repeat (Marcand et al. 1997).”
Arnerić, M., & Lingner, J. (2007) · EMBO Reports · doi:10.1038/sj.embor.7401082 · Cited by 98
“…the telomere and create a negative feedback loop that regulates telomerase in a length-dependent manner (Kyrion et al, 1992; Krauskopf & Blackburn, 1996; Marcand et al, 1997; Wotton & Shore, 1997; Teixeira et al, 2004), but how this regulatory signal is transmitted to telomerase is not yet known.”
BackgroundInfluentialHuman telomere length is chromosome end–specific and conserved across individuals
Karimian, K., Groot, A. C. G.-D., Huso, V. L., Kahidi, R., Tan, K., Sholes, S. L., Keener, R., McDyer, J. F., Alder, J. K., Li, H., et al. (2024) · Science · doi:10.1126/science.ado0431 · Cited by 97
Craven, R. J., & Petes, T. D. (1999) · Genetics · doi:10.1093/genetics/152.4.1531 · Cited by 94
Telomere maintenance and DNA replication: how closely are these two connected?
Chakhparonian, M., & Wellinger, R. J. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00135-5 · Cited by 95
“This regulation is thought to operate through a ‘counting mechanism’, which establishes the maximal length of the tract added by TDR [ 68 ].”
BackgroundSolving the Telomere Replication Problem
Maestroni, L., Matmati, S., & Coulon, S. (2017) · Genes · doi:10.3390/genes8020055 · Cited by 94
“The telomere-counting model has been proposed to explain stochastic telomere length elongation by telomerase at short telomeres [118].”
Shen, M., Haggblom, C., Vogt, M., Hunter, T. R., & Lu, K. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13618 · Cited by 95
Molecular Recognition of Protein Surfaces: High Affinity Ligands for the CBP KIX Domain
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Shore, D. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00178-7 · Cited by 93
Self-citationNegrini, S., Ribaud, V., Bianchi, A., & Shore, D. (2007) · Genes & Development · doi:10.1101/gad.400907 · Cited by 101
“In several systems evidence has been presented indicating the involvement of TG-repeat-binding proteins in a negative feedback mechanism controlling telomerase recruitment and/or action in cis at the telomere (Marcand et al. 1997; van Steensel and de Lange 1997; Ray and Runge 1999).”
BackgroundSelf-citationTelomeres and telomerase as targets for anticancer drug development
Olaussen, K. A., Dubrana, K., Dômont, J., Spano, J., Sabatier, L., & Soria, J. (2006) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2005.08.007 · Cited by 96
The Dynamics of Yeast Telomeres and Silencing Proteins through the Cell Cycle
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Linger, B. R., & Price, C. M. (2009) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409230903307329 · Cited by 97
“The C-terminal domain of Rap1 then recruits two additional proteins, Rif1 and Rif2, which are responsible for telomere length regulation (Marcand et al., 1997).”
Mattern, K. A., Swiggers, S. J. J., Nigg, A. L., Löwenberg, B., Houtsmuller, A. B., & Zijlmans, J. M. J. M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5587-5594.2004 · Cited by 92
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BackgroundBucholc, M., Park, Y., & Lustig, A. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6559-6573.2001 · Cited by 90
“The number of bound Rap1p C termini, or of factors associating with the C termini, is counted through an as-yetunknown mechanism, until an optimal stable length is reached (44, 61).”
BackgroundEversole, A., & Maizels, N. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.15.5425-5432.2000 · Cited by 91
Bertuch, A. A., & Lundblad, V. (2004) · Genetics · doi:10.1534/genetics.166.4.1651 · Cited by 97
Ray, A., & Runge, K. W. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.31 · Cited by 88
“showed that internal TG1-3 sequences or fusion proteins containing the Gal4p DNA binding domain and the Rap1p C terminus tethered internal to the terminal TG1-3 tract could cause telomeres to be maintained at a shorter equilibrium length (29).”
BackgroundInfluentialPlatt, J. M., Ryvkin, P., Wanat, J. J., Donahue, G., Ricketts, M. D., Barrett, S. P., Waters, H. J., Song, S., Chavez, A., Abdallah, K. O., et al. (2013) · Genes & Development · doi:10.1101/gad.218776.113 · Cited by 89
“At telomeres, Rap1 contributes to capping and length regulation, localization to the nuclear periphery, and formation of heterochromatin (Klein et al. 1992; Kyrion et al. 1993; Palladino et al. 1993; Marcand et al. 1997; Pardo and Marcand 2005; Negrini et al. 2007; Vodenicharov et al. 2010).”
BackgroundRegulating telomere length from the inside out: the replication fork modelPreprint
Greider, C. W. (2016) · Genes & Development · doi:10.1101/gad.280578.116 · Cited by 90
“Several experimental findings helped establish the “protein-counting” model for telomere length regulation (Marcand et al. 1997).”
BackgroundMethodResultInfluentialTrypanosome Telomeres Are Protected by a Homologue of Mammalian TRF2
Li, B., Espinal, A., & Cross, G. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.12.5011-5021.2005 · Cited by 87
“mere length and protects chromosome ends (13, 46), it is not a”
BackgroundHipHop interacts with HOAP and HP1 to protect Drosophila telomeres in a sequence‐independent manner
Gao, G., Walser, J., Beaucher, M., Morciano, P., Wesolowska, N., Chen, J., & Rong, Y. S. (2010) · The EMBO Journal · doi:10.1038/emboj.2009.394 · Cited by 85
Telomeres, the nucleolus and aging
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Comparative biology of telomeres: Where plants stand
Watson, J. M., & Říha, K. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.06.017 · Cited by 86
“Regulation of telomerase activity at the telomere is much more complicated, likely involving multiple proteins and a negative feedback loop such as the protein counting mechanism discovered in yeast [35].”
BackgroundLength-dependent processing of telomeres in the absence of telomerase
Fallet, E., Jolivet, P., Soudet, J., Lisby, M., Gilson, É., & Teixeira, M. T. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1328 · Cited by 86
Armstrong, C. A., & Tomita, K. (2017) · Open Biology · doi:10.1098/rsob.160338 · Cited by 83
Hediger, F., Dubrana, K., & Gasser, S. M. (2002) · Journal of Structural Biology · doi:10.1016/s1047-8477(02)00533-6 · Cited by 80
“The Rap1p–Rif1/2 pathway senses the length of the telomeric TG1–3 repeat through Rap1 binding sites and restricts telomere length through a feedback inhibition of telomerase (Marcand et al., 1997).”
BackgroundMolecular Basis for Telomere Repeat Divergence in Budding Yeast
Förstemann, K., & Lingner, J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.21.7277-7286.2001 · Cited by 84
“Genome sequence 3 (3) 25 (24) 39 (37) 19 (18) 14 (13) 1.”
Telomere capping in non‐dividing yeast cells requires Yku and Rap1
Vodenicharov, M. D., Laterreur, N., & Wellinger, R. J. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.155 · Cited by 87
“Earlier work had established that Rap1 is a negative regulator of telomerase (Marcand et al, 1997) and inhibitor of NHEJ (Pardo and Marcand, 2005).”
BackgroundZinc-binding proteins (metallothionein and α-2 macroglobulin) and immunosenescence
Mocchegiani, E., Costarelli, L., Giacconi, R., Cipriano, C., Muti, E., & Malavolta, M. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.08.010 · Cited by 79
Telomere Length Regulation and Telomeric Chromatin Require the Nonsense-Mediated mRNA Decay Pathway
Lew-Smith, J., Enomoto, S., & Berman, J. G. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.10.6121 · Cited by 80
“In the yeast Saccharomyces cerevisiae, the most abundant telomere-binding protein, repressor activator protein (Rap1p) (9, 53, 80), binds double-stranded telomere repeats and is required for both telomeric silencing (43, 83) and telomere length regulation (59, 61, 83).”
BackgroundGasser, S. M. (2000) · Science · doi:10.1126/science.288.5470.1377 · Cited by 77
Redundancy principle and the role of extreme statistics in molecular and cellular biology
Schuss, Z., Basnayake, K., & Holcman, D. (2019) · Physics of Life Reviews · doi:10.1016/j.plrev.2019.01.001 · Cited by 77
“Telomeres are necessary for the maintenance of chromosomal integrity and overall genomic stability [26,62] and in the absence of any mechanism of elongation, telomere length can only decrease over time [95].”
BackgroundTelomere regulation and function during meiosis
Siderakis, M., & Tarsounas, M. (2007) · Chromosome Research · doi:10.1007/s10577-007-1149-7 · Cited by 81
“…generation Tercj/j mice are significantly reduced compared to wild type (Franco et al. 2002), consistent with the idea that the amount of TRF1 at each telomere reflects the length of the telomeric tract, similarly to the telomere repeat counting role of Rap1 in budding yeast (Marcand et al. 1997).”
BackgroundModulation of telomerase activity by telomere DNA-binding proteins in OxytrichaPreprint
Froelich-Ammon, S. J., Dickinson, B., Bevilacqua, J. M., Schultz, S. C., & Cech, T. R. (1998) · Genes & Development · doi:10.1101/gad.12.10.1504 · Cited by 72
Coordinate Regulation of G- and C Strand Length during New Telomere Synthesis
Fan, X., & Price, C. M. (1997) · Molecular Biology of the Cell · doi:10.1091/mbc.8.11.2145 · Cited by 70
“One general theme to emerge is that telomere proteins such as Rap1, Rif1, Rif2, Cdc13, and Est1 set up a complex chromatin structure that regulates telomerase access to the DNA terminus (Zakian, 1995; Krauskopf and Blackburn, 1996; Cooper et al., 1997; Marcand et al., 1997).”
BackgroundAssessment of telomere length and factors that contribute to its stability
Saldanha, S. N., Andrews, L. G., & Tollefsbol, T. O. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03410.x · Cited by 69
Subtelomeric proteins negatively regulate telomere elongation in budding yeast
Berthiau, A.-S., Yankulov, K., Bah, A., Revardel, E., Luciano, P., Wellinger, R. J., Géli, V., & Gilson, É. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600975 · Cited by 69
“As control, we used the Gbd-Rap1 hybrid containing the C-terminus of Rap1 (amino acids 653–827) (Marcand et al, 1997).”
BackgroundMethodInfluentialHanaoka, S., Nagadoi, A., Yoshimura, S., Aimoto, S., Li, B., de Lange, T., & Nishimura, Y. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4924 · Cited by 74
Sequence‐specific binding property of Arabidopsis thaliana telomeric DNA binding protein 1 (AtTBP1)
Hwang, M. G., Chung, I. K., Kang, B. G., & Cho, M. H. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02685-0 · Cited by 68
Sholes, S. L., Karimian, K., Gershman, A., Kelly, T. J., Timp, W., & Greider, C. W. (2021) · Genome Research · doi:10.1101/gr.275868.121 · Cited by 73
“This combined with other observations (Marcand et al. 1997) has led to establishment of a “protein counting” model, where telomerase is proposed to preferentially elongate short telomeres while ignoring long ones.”
ResultMatsuura, A., Naito, T., & Ishikawa, F. (1999) · Genetics · doi:10.1093/genetics/152.4.1501 · Cited by 68
Stampfer, M. R., Bodnar, A. G., Garbe, J. C., Wong, M. P., Pan, A., Villeponteau, B., & Yaswen, P. (1997) · Molecular Biology of the Cell · doi:10.1091/mbc.8.12.2391 · Cited by 69
“Although unicellular organisms such as yeast express telomerase activity, this activity is regulated to maintain control of telomere length within a set range (Krauskopf and Blackburn, 1996; Cooper et al., 1997; Marcand et al., 1997).”
BackgroundTelomeres and chromosomal instability
Mathieu, N., Pirzio, L. M., Freulet-Marrière, M.-A., Desmaze, C., & Sabatier, L. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3296-0 · Cited by 69
Deletion of Ogg1 DNA glycosylase results in telomere base damage and length alteration in yeast
Lü, J., & Liu, Y. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.355 · Cited by 72
“Several studies have reported that the number of Rap1p–Rif1p–Rif2p complex molecules at telomeres adversely influences telomere length in a telomerase-dependent manner (Marcand et al, 1997, 1999; Wotton and Shore, 1997; Ray and Runge, 1999; Levy and Blackburn, 2004; Teixeira et al, 2004).”
BackgroundChromosome ends: different sequences may provide conserved functions
Louis, E. J., & Vershinin, A. V. (2005) · BioEssays · doi:10.1002/bies.20259 · Cited by 68
“This hypothesis is based on the socalled protein ‘counting’ model where Rap1 is part of a system that measures telomere length, possibly by forming numberdependent complexes between the C-terminal domain of Rap1 with the interacting proteins Rif1p and Rif2p.((75)) Longer telomeres have more DNA-binding sites for Rap1…”
InfluentialTelomeres, telomerase, and stability of the plant genome
McKnight, T. D., Říha, K., & Shippen, D. E. (2002) · Plant Molecular Biology · doi:10.1023/a:1014091032750 · Cited by 65
“appropriate amount of telomere-bound protein (Marcand et al., 1997).”
BackgroundTelomere maintenance, function and evolution: the yeast paradigm
Teixeira, M. T., & Gilson, É. (2005) · Chromosome Research · doi:10.1007/s10577-005-0999-0 · Cited by 65
“These mediate the so-called protein counting mechanism: an increasing number of Rap1YRif telomere bound complexes, which are proportional to the double stranded telomere tract, inhibit telomerase activity ( Marcand et al. 1997, 1999 ).”
BackgroundThe Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae
Hass, E. P., & Zappulla, D. C. (2015) · eLife · doi:10.7554/elife.07750 · Cited by 61
“Rif proteins – negative regulators of telomerase – leads to increased telomerase recruitment at short telomeres (Marcand et al., 1997; Levy and Blackburn, 2004; Teixeira et al., 2004; Bianchi and Shore, 2007).”
BackgroundInfluentialTelomerase and telomere-binding proteins: Controlling the endgame
Shore, D. (1997) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(97)01082-7 · Cited by 62
Self-citationA Plant Gene Encoding a Myb-like Protein That Binds Telomeric GGTTTAG Repeats in Vitro
Chen, C. M., Wang, C. T., & Ho, C. H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009659200 · Cited by 60
Solution structure of the DNA-binding domain of human telomeric protein, hTRF1
Nishikawa, T., Nagadoi, A., Yoshimura, S., Aimoto, S., & Nishimura, Y. (1998) · Structure · doi:10.1016/s0969-2126(98)00106-3 · Cited by 62
Dubrana, K., Perrod, S., & Gasser, S. M. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00210-6 · Cited by 59
Subtelomeric Transcription and its Regulation
Kwapisz, M., & Morillon, A. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.01.026 · Cited by 64
Hypermethylation of yeast telomerase RNA by the snRNA and snoRNA methyltransferase Tgs1
Franke, J., Gehlen, J., & Ehrenhofer‐Murray, A. E. (2008) · Journal of Cell Science · doi:10.1242/jcs.033308 · Cited by 59
“Rap1 is a key component of telomere length regulation and controls Journal of Cell Science 121 (21) Jo ur na l o f C el l S ci en ce 3555Hypermethylation of yeast telomerase RNA by Tgs1 telomere extension by a ‘protein-counting mechanism’ (Marcand et al., 1997).”
BackgroundInfluentialAdapting machine-learning algorithms to design gene circuits
Hiscock, T. W. (2019) · BMC Bioinformatics · doi:10.1186/s12859-019-2788-3 · Cited by 69
Telomeric armor: the layers of end protection
Oganesian, L., & Karlseder, J. (2009) · Journal of Cell Science · doi:10.1242/jcs.050567 · Cited by 61
“, 2000), known to play a key role in regulation of telomere length (Marcand et al., 1997).”
BackgroundTsai, Y.-L., Tseng, S., Chang, S.-H., Lin, C., & Teng, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.16.5679-5687.2002 · Cited by 60
“The copy number of the Rap1p complex negatively regulates telomere length (31, 51).”
BackgroundKishi, S., Wulf, G. M., Nakamura, M., & Lu, K. P. (2001) · Oncogene · doi:10.1038/sj.onc.1204229 · Cited by 58
“For example, homeostasis of telomere length in budding and ®ssion yeast cells requires the telomeric proteins Rap1p and Taz1, respectively (Cooper et al., 1997; Krauskopf and Blackburn, 1996; Marcand et al., 1997).”
BackgroundTelomere Rapid Deletion Regulates Telomere Length in Arabidopsis thaliana
Watson, J. M., & Shippen, D. E. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02059-06 · Cited by 58
“The protein counting model posits that the primary means of telomere length regulation is through an ability to “count” the number of telomeric binding proteins (37).”
BackgroundTelomere length measurement by Q-FISH
Slijepčević, P. (2001) · Springer eBooks · doi:10.1007/978-94-010-0330-8_3 · Cited by 57
“A similar mechanism has been described in yeast [ 14 ].”
BackgroundRap1 protein regulates telomere turnover in yeast
Krauskopf, A., & Blackburn, E. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12486 · Cited by 57
Metadata
- Authors
- Marcand, S., Gilson, E., & Shore, D.
- Affiliations
- École Normale Supérieure de Lyon (FR)
- E. Gilson, Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure de Lyon, UMR49 CNRS/ENSL, 69364 Lyon Cédex 07, France.
- University of Geneva (CH)
- Corresponding author
- Marcand, Stéphane
- Shore, David
- Venue
- Science
- Published
- 1997-02-14
- Volume
- 275
- Issue
- 5302
- Pages
- 986-990
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1978002329
- Cited by
- 524
- References
- 38
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 14 · 2020: 5 · 2019: 17 · 2018: 10 · 2017: 12 · 2016: 13 · 2015: 9 · 2014: 14 · 2013: 14 · 2012: 10
- FWCI
- 23.60
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5r01gm040094-09)
- National Institute of General Medical Sciences (GM 40094)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- telomere length regulation, Rap1p, feedback regulation, protein-DNA interactions, telomere elongation, Saccharomyces cerevisiae, telomere shortening
- MeSH terms
- Binding Sites, Fungal Proteins, Genetic Markers, Mutation, Saccharomyces cerevisiae, Transformation, Genetic, Chromosomes, Fungal, Gene Expression Regulation, Fungal, Telomere, Telomerase, GTP-Binding Proteins, rap GTP-Binding Proteins
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