Genomes and Genes
telomere binding proteins
Summary: Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.
- Surovtseva Y, Shakirov E, Vespa L, Osbun N, Song X, Shippen D. Arabidopsis POT1 associates with the telomerase RNP and is required for telomere maintenance. EMBO J. 2007;26:3653-61 pubmed
- Oza P, Jaspersen S, Miele A, Dekker J, Peterson C. Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev. 2009;23:912-27 pubmed publisher..Based on these findings, we propose that sequestration of unrepaired or slowly repaired DSBs to the nuclear periphery reflects a competition between alternative repair pathways. ..
- Larrivée M, Wellinger R. Telomerase- and capping-independent yeast survivors with alternate telomere states. Nat Cell Biol. 2006;8:741-7 pubmed..Chromosome capping, therefore, is not strictly dependent on canonical capping proteins, such as Cdc13p, but can be achieved by alternate mechanisms. ..
- Bianchi A, Shore D. Early replication of short telomeres in budding yeast. Cell. 2007;128:1051-62 pubmed..These data reveal an epigenetic effect of telomere length on the activity of nearby replication origins and an unanticipated link between telomere replication timing and telomerase action. ..
- Levy D, Blackburn E. Counting of Rif1p and Rif2p on Saccharomyces cerevisiae telomeres regulates telomere length. Mol Cell Biol. 2004;24:10857-67 pubmed..We propose that a nucleation and spreading mechanism is involved in forming the higher-order telomere structure that regulates telomere length. ..
- Wellinger R. The CST complex and telomere maintenance: the exception becomes the rule. Mol Cell. 2009;36:168-9 pubmed publisher..In this issue of Molecular Cell, Miyake et al. (2009) and Surovtseva et al. (2009) provide evidence that these complexes coexist and function at telomeres in many species. ..
- Yarragudi A, Miyake T, Li R, Morse R. Comparison of ABF1 and RAP1 in chromatin opening and transactivator potentiation in the budding yeast Saccharomyces cerevisiae. Mol Cell Biol. 2004;24:9152-64 pubmed..These results indicate that ABF1 and RAP1 achieve functional similarity in part via mechanistically distinct pathways. ..
- Houghtaling B, Cuttonaro L, Chang W, Smith S. A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr Biol. 2004;14:1621-31 pubmed..Our findings suggest a dynamic cross talk between TRF1 and TRF2 and provide a molecular mechanism for telomere length homeostasis by TRF2 in the absence of TRF1. ..
- Ye J, Hockemeyer D, Krutchinsky A, Loayza D, Hooper S, Chait B, et al. POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev. 2004;18:1649-54 pubmed..Reduction of PIP1 or POT1 levels with shRNAs led to telomere elongation, indicating that PIP1 contributes to telomere length control through recruitment of POT1. ..
- Vega L, Mateyak M, Zakian V. Getting to the end: telomerase access in yeast and humans. Nat Rev Mol Cell Biol. 2003;4:948-59 pubmed
- Arnoult N, Saintome C, Ourliac Garnier I, Riou J, Londono Vallejo A. Human POT1 is required for efficient telomere C-rich strand replication in the absence of WRN. Genes Dev. 2009;23:2915-24 pubmed publisher..Our study reveals an unanticipated role for hPOT1 during telomere replication. ..
- Tomita K, Cooper J. The telomere bouquet controls the meiotic spindle. Cell. 2007;130:113-26 pubmed..This discovery illuminates an unanticipated level of communication between chromosomes and the spindle apparatus that may be widely conserved among eukaryotes. ..
- Chen Y, Yang Y, Van Overbeek M, Donigian J, Baciu P, de Lange T, et al. A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science. 2008;319:1092-6 pubmed publisher..Conversely, the TRFH domain of TRF1, but not of TRF2, interacts with another shelterin-associated factor: PinX1. ..
- Li B, de Lange T. Rap1 affects the length and heterogeneity of human telomeres. Mol Biol Cell. 2003;14:5060-8 pubmed..Surprisingly, hRap1 alleles lacking the BRCT domain diminished the heterogeneity of human telomeres, indicating that hRap1 also plays a role in the regulation of telomere length distribution. ..
- Davis L, Smith G. The meiotic bouquet promotes homolog interactions and restricts ectopic recombination in Schizosaccharomyces pombe. Genetics. 2006;174:167-77 pubmed..We discuss mechanisms by which the bouquet may prevent deleterious translocations by restricting ectopic recombination. ..
- Savage S, Giri N, Baerlocher G, Orr N, Lansdorp P, Alter B. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet. 2008;82:501-9 pubmed publisher..This represents the first shelterin complex mutation linked to human disease and confirms the role of very short telomeres as a diagnostic test for DC. ..
- Anderson C, Korkin D, Smith D, Makovets S, Seidel J, Sali A, et al. Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break. Genes Dev. 2008;22:854-9 pubmed publisher..Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases. ..
- Paeschke K, Juranek S, Simonsson T, Hempel A, Rhodes D, Lipps H. Telomerase recruitment by the telomere end binding protein-beta facilitates G-quadruplex DNA unfolding in ciliates. Nat Struct Mol Biol. 2008;15:598-604 pubmed publisher..These observations allow us to propose a model for the regulation of G-quadruplex unfolding and telomere synthesis during the cell cycle. ..
- Fajkus J, Sykorova E, Leitch A. Telomeres in evolution and evolution of telomeres. Chromosome Res. 2005;13:469-79 pubmed..We describe how telomere dysfunction, resulting in end-to-end chromosome fusions, can have a profound effect on chromosome evolution and perhaps even speciation. ..
- Puglisi A, Bianchi A, Lemmens L, Damay P, Shore D. Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition. EMBO J. 2008;27:2328-39 pubmed publisher..These data provide new insights into the coordination of telomere capping and telomerase regulation. ..
- Veldman T, Etheridge K, Counter C. Loss of hPot1 function leads to telomere instability and a cut-like phenotype. Curr Biol. 2004;14:2264-70 pubmed..We conclude that hPot1 protects chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. ..
- Tseng S, Lin J, Teng S. The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res. 2006;34:6327-36 pubmed..These results demonstrate the telomerase recruitment domain of Cdc13p as an important new telomere-specific target of Mec1p/Tel1p. ..
- Xin H, Liu D, Songyang Z. The telosome/shelterin complex and its functions. Genome Biol. 2008;9:232 pubmed publisher..A complex of six telomere-associated proteins has been identified--the telosome or shelterin complex--that is crucial for both the maintenance of telomere structure and its signaling functions. ..
- Tani A, Murata M. Alternative splicing of Pot1 (Protection of telomere)-like genes in Arabidopsis thaliana. Genes Genet Syst. 2005;80:41-8 pubmed..By western blot analysis, we found that the antibody made against the N-terminal amino acids of AtPOT1-1 recognized three different polypeptides, indicating that all three variants are being translated in Arabidopsis. ..
- Walne A, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood. 2008;112:3594-600 pubmed publisher..In this large series, TINF2 mutations account for approximately 11% of all DC, but they do not play a significant role in patients with related disorders. This study emphasises the role of defective telomere maintenance on human disease...
- Schmitt J, Benavente R, Hodzic D, Hoog C, Stewart C, Alsheimer M. Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope. Proc Natl Acad Sci U S A. 2007;104:7426-31 pubmed..Together with recent findings in fission yeast, our study indicates that the molecular mechanisms required for tethering meiotic telomeres and their dynamic movements during bouquet formation are conserved among eukaryotes. ..
- Lei K, Zhang X, Ding X, Guo X, Chen M, Zhu B, et al. SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice. Proc Natl Acad Sci U S A. 2009;106:10207-12 pubmed publisher..These results clearly indicate that SUN1 and SUN2 function critically in skeletal muscle cells for Syne-1 localization at the NE, which is essential for proper myonuclear positioning. ..
- Sarthy J, Bae N, Scrafford J, Baumann P. Human RAP1 inhibits non-homologous end joining at telomeres. EMBO J. 2009;28:3390-9 pubmed publisher..These results provide the first evidence that hRAP1 inhibits NHEJ at mammalian telomeres and identify hRAP1 as a mediator of genome stability. ..
- Surovtseva Y, Churikov D, Boltz K, Song X, Lamb J, Warrington R, et al. Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Mol Cell. 2009;36:207-18 pubmed publisher..These data indicate that CTC1 participates in telomere maintenance in diverse species and that a CST-like complex is required for telomere integrity in multicellular organisms. ..
- Adams I, McLaren A. Identification and characterisation of mRif1: a mouse telomere-associated protein highly expressed in germ cells and embryo-derived pluripotent stem cells. Dev Dyn. 2004;229:733-44 pubmed..mRif1 may be involved in the maintenance of telomere length or pluripotency in the germline and during early mouse development. ..
- Miyoshi T, Kanoh J, Saito M, Ishikawa F. Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length. Science. 2008;320:1341-4 pubmed publisher..Such molecular architectures are similar to those of mammalian shelterin, indicating that the overall DNA-protein architecture is conserved across evolution. ..
- Addinall S, Downey M, Yu M, Zubko M, Dewar J, Leake A, et al. A genomewide suppressor and enhancer analysis of cdc13-1 reveals varied cellular processes influencing telomere capping in Saccharomyces cerevisiae. Genetics. 2008;180:2251-66 pubmed publisher..The high-throughput spot-testing approach that we describe is generally applicable and could aid in understanding other aspects of eukaryotic cell biology. ..
- Miyake Y, Nakamura M, Nabetani A, Shimamura S, Tamura M, Yonehara S, et al. RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol Cell. 2009;36:193-206 pubmed publisher..We propose that CST is a replication protein A (RPA)-like complex that is not directly involved in conventional DNA replication at forks but plays a role in DNA metabolism frequently required by telomeres. ..
- Takai H, Wang R, Takai K, Yang H, de Lange T. Tel2 regulates the stability of PI3K-related protein kinases. Cell. 2007;131:1248-59 pubmed..These data identify Tel2 as a highly conserved regulator of PIKK stability. ..
- Kaminker P, Plachot C, Kim S, Chung P, Crippen D, Petersen O, et al. Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2. J Cell Sci. 2005;118:1321-30 pubmed..Here we show that a novel extra-telomeric organization of TIN2 is associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation. ..
- Palm W, Hockemeyer D, Kibe T, de Lange T. Functional dissection of human and mouse POT1 proteins. Mol Cell Biol. 2009;29:471-82 pubmed publisher..Thus, human POT1 combines the features of POT1a and POT1b. ..
- Gao H, Cervantes R, Mandell E, Otero J, Lundblad V. RPA-like proteins mediate yeast telomere function. Nat Struct Mol Biol. 2007;14:208-14 pubmed..Identification of an RPA-like complex that is targeted to a specific region of the genome suggests that multiple RPA-like complexes have evolved, each making individual contributions to genomic stability. ..
- Sowd G, Lei M, Opresko P. Mechanism and substrate specificity of telomeric protein POT1 stimulation of the Werner syndrome helicase. Nucleic Acids Res. 2008;36:4242-56 pubmed publisher..Collectively, these data suggest POT1 promotes the apparent processivity of WRN helicase by maintaining partially unwound strands in a melted state, rather than preventing WRN dissociation from the substrate. ..
- Wang F, Podell E, Zaug A, Yang Y, Baciu P, Cech T, et al. The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature. 2007;445:506-10 pubmed..We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension. ..
- Foster S, Zubko M, Guillard S, Lydall D. MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants. DNA Repair (Amst). 2006;5:840-51 pubmed..Instead, we find that Rad50 inhibits ssDNA accumulation and promotes cdc13-1 cell viability, consistent with a major role for MRX in telomere capping. ..
- de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100-10 pubmed..Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1. ..
- Miller K, Ferreira M, Cooper J. Taz1, Rap1 and Rif1 act both interdependently and independently to maintain telomeres. EMBO J. 2005;24:3128-35 pubmed..Thus, Rap1 and Rif1 are each required for a subset of the functions of Taz1, but each acquires Taz1-independent functions in its absence. Furthermore, Taz1 can function independently of its known binding partners. ..
- Trujillo K, Bunch J, Baumann P. Extended DNA binding site in Pot1 broadens sequence specificity to allow recognition of heterogeneous fission yeast telomeres. J Biol Chem. 2005;280:9119-28 pubmed..Consistent with a role in chromosome end capping, Pot1 prevents access of telomerase to the 3'-end and protects against exonucleolytic degradation. ..
- Lei M, Podell E, Cech T. Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol. 2004;11:1223-9 pubmed..pombe Pot1pN-ssDNA complex, whereas the second OB fold binds and protects the 3' end of the ssDNA. These results provide an atomic-resolution model for chromosome end-capping. ..
- Chiang Y, Kim S, Tessarollo L, Campisi J, Hodes R. Telomere-associated protein TIN2 is essential for early embryonic development through a telomerase-independent pathway. Mol Cell Biol. 2004;24:6631-4 pubmed..Our findings suggest that TIN2 has a role independent of telomere length regulation that is essential for embryonic development and cell viability. ..
- Wei C, Price C. Cell cycle localization, dimerization, and binding domain architecture of the telomere protein cPot1. Mol Cell Biol. 2004;24:2091-102 pubmed..This second motif could be another OB fold. Although dimerization is inefficient in vitro, it may be regulated in vivo and could promote association with other telomere proteins and/or telomere compaction. ..
- Deng Z, Atanasiu C, Burg J, Broccoli D, Lieberman P. Telomere repeat binding factors TRF1, TRF2, and hRAP1 modulate replication of Epstein-Barr virus OriP. J Virol. 2003;77:11992-2001 pubmed..These results indicate that TRF2 and hRap1 promote, while TRF1 antagonizes, OriP-dependent DNA replication and suggest that these telomeric factors contribute to the establishment of replication competence at OriP. ..
- Marcand S, Pardo B, Gratias A, Cahun S, Callebaut I. Multiple pathways inhibit NHEJ at telomeres. Genes Dev. 2008;22:1153-8 pubmed publisher..We discuss a possible mechanism that would explain Rif2 multifunctionality at telomeres and the recent evolutionary origin of Rif2 from an origin recognition complex (ORC) subunit. ..
- Cristofari G, Sikora K, Lingner J. Telomerase unplugged. ACS Chem Biol. 2007;2:155-8 pubmed..Two recent papers identify TPP1 as a critical mediator of this control. TPP1 forms part of the telomeric shelterin complex while also associating with telomerase, stimulating its activity and processivity. ..
- Li S, Makovets S, Matsuguchi T, Blethrow J, Shokat K, Blackburn E. Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression. Cell. 2009;136:50-61 pubmed publisher..These results provide a direct mechanistic link between coordination of telomere elongation and cell-cycle progression in vivo. ..
- Kuchar M, Fajkus J. Interactions of putative telomere-binding proteins in Arabidopsis thaliana: identification of functional TRF2 homolog in plants. FEBS Lett. 2004;578:311-5 pubmed..In humans, the TRF1-complex recruits hPot1 to telomeres by protein-protein interactions where it is involved in telomere length regulation. Possibly, AtTRB1 has a similar role in recruiting AtPot1. ..
- Xu L, Blackburn E. Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules. J Cell Biol. 2004;167:819-30 pubmed..In telophase, hRif1 localized to chromosomes, and in interphase, it was intranuclear. These results define a novel subcellular localization behavior for hRif1 during the cell cycle. ..
- Bianchi A, Negrini S, Shore D. Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdc13 and Est1. Mol Cell. 2004;16:139-46 pubmed..These data demonstrate a critical role for Est1 in recruiting telomerase to its site of action, in cooperation with the telomere binding protein Cdc13. ..