Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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Telo_bind Telomeric single stranded DNA binding POT1/CDC13

SMART accession number:	SM00976
Description:	The telomere-binding protein forms a heterodimer in ciliates consisting of an alpha and a beta subunit. This complex may function as a protective cap for the single-stranded telomeric overhang. Alpha subunit consists of 3 structural domains, all with the same beta-barrel OB fold.
Interpro abstract (IPR011564):	This entry represents a domain that binds single stranded telomeric DNA and adopts an OB fold [(PUBMED:11935027)]. It includes the proteins POT1 and CDC13 which have been shown to regulate telomere length, replication and capping [(PUBMED:11230149), (PUBMED:18066078), (PUBMED:16943437)].
GO process:	telomere maintenance (GO:0000723)
GO component:	nuclear chromosome, telomeric region (GO:0000784)
GO function:	DNA binding (GO:0003677)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 138 Telo_bind domains in 138 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a Telo_bind domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with Telo_bind domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Arabidopsis thaliana, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Cellular role: chromatin
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Churikov D, Price CM
  • Pot1 and cell cycle progression cooperate in telomere length regulation.
  • Nat Struct Mol Biol. 2008; 15: 79-84
  • Display abstract

  • Removal of the vertebrate telomere protein Pot1 results in a DNA damageresponse and cell cycle arrest. Here we show that loss of chicken Pot1causes Chk1 activation, and inhibition of Chk1 signaling prevents the cellcycle arrest. However, arrest still occurs after disruption of ATM, whichencodes another DNA damage response protein. These results indicate thatPot1 is required to prevent a telomere checkpoint mediated by another suchprotein, ATR, that is most likely triggered by the G-overhang. We alsoshow that removal of Pot1 causes exceptionally rapid telomere growth uponarrest in late S/G2 of the cell cycle. However, release of the arrestslows both telomere growth and G-overhang elongation. Thus, Pot1 seems toregulate telomere length and G-overhang processing both through directinteraction with the telomere and by preventing a late S/G2 delay in thecell cycle. Our results reveal that cell cycle progression is an importantcomponent of telomere length regulation.

  • Churikov D, Wei C, Price CM
  • Vertebrate POT1 restricts G-overhang length and prevents activation of atelomeric DNA damage checkpoint but is dispensable for overhangprotection.
  • Mol Cell Biol. 2006; 26: 6971-82
  • Display abstract

  • Although vertebrate POT1 is thought to play a role in both telomerecapping and length regulation, its function has proved difficult toanalyze. We therefore generated a conditional cell line that lackswild-type POT1 but expresses an estrogen receptor-POT1 fusion. The cellsgrow normally in tamoxifen, but drug removal causes loss of POT1 from thetelomere, rapid cell cycle arrest, and eventual cell death. The arrestedcells have a 4N DNA content, and addition of caffeine causes immediateentry into mitosis, suggesting a G(2) arrest due to an ATM- and/orATR-mediated checkpoint. gammaH2AX accumulates at telomeres, indicating atelomeric DNA damage response, the likely cause of the checkpoint.However, POT1 loss does not cause degradation of the G-strand overhang.Instead, the amount of G overhang increases two- to threefold. Some cellseventually escape the cell cycle arrest and enter mitosis. They rarelyexhibit telomere fusions but show severe chromosome segregation defectsdue to centrosome amplification. Our data indicate that vertebrate POT1 isrequired for telomere capping but that it functions quite differently fromTRF2. Instead of being required for G-overhang protection, POT1 isrequired to suppress a telomeric DNA damage response. Our results alsoindicate significant functional similarities between POT1 and Cdc13 frombudding yeast (Saccharomyces cerevisiae).

  • Mitton-Fry RM, Anderson EM, Hughes TR, Lundblad V, Wuttke DS
  • Conserved structure for single-stranded telomeric DNA recognition.
  • Science. 2002; 296: 145-7
  • Display abstract

  • The essential Cdc13 protein in the yeast Saccharomyces cerevisiae is asingle-stranded telomeric DNA binding protein required for chromosome endprotection and telomere replication. Here we report the solution structureof the Cdc13 DNA binding domain in complex with telomeric DNA. Thestructure reveals the use of a single OB (oligonucleotide/oligosaccharidebinding) fold augmented by an unusually large loop for DNA recognition.This OB fold is structurally similar to OB folds found in the ciliatedprotozoan telomere end-binding protein, although no sequence similarity isapparent between them. The common usage of an OB fold for telomeric DNAinteraction demonstrates conservation of end-protection mechanisms amongeukaryotes.

  • Chandra A, Hughes TR, Nugent CI, Lundblad V
  • Cdc13 both positively and negatively regulates telomere replication.
  • Genes Dev. 2001; 15: 404-14
  • Display abstract

  • Cdc13 is a single-strand telomeric DNA-binding protein that positivelyregulates yeast telomere replication by recruiting telomerase tochromosome termini through a site on Cdc13 that is eliminated by thecdc13-2 mutation. Here we show that Cdc13 has a separate role in negativeregulation of telomere replication, based on analysis of a new mutation,cdc13-5. Loss of this second regulatory activity results in extensiveelongation of the G strand of the telomere by telomerase, accompanied by areduced ability to coordinate synthesis of the C strand. Both the cdc13-5mutation and DNA polymerase alpha mutations (which also exhibit elongatedtelomeres) are suppressed by increased expression of the Cdc13-interactingprotein Stn1, indicating that Stn1 coordinates action of the laggingstrand replication complex with the regulatory activity of CDC13. However,the association between Cdc13 and Stn1 is abolished by cdc13-2, the samemutation that eliminates the interaction between Cdc13 and telomerase. Wepropose that Cdc13 participates in two regulatory steps-first positive,then negative-as a result of successive binding of telomerase and thenegative regulator Stn1 to overlapping sites on Cdc13. Thus, Cdc13coordinates synthesis of both strands of the telomere by first recruitingtelomerase and subsequently limiting G-strand synthesis by telomerase inresponse to C-strand replication.

• Structure (3D structures containing this domain)

• 3D Structures of Telo_bind domains in PDB

  PDB code	Main view	Title
  1jb7		Dna g-quartets in a 1.86 a resolution structure of an oxytricha nova telomeric protein-dna complex
  1k8g		Crystal structure of the n-terminal domain of oxytricha nova telomere end binding protein alpha subunit both uncomplexed and complexed with telomeric ssdna
  1kix		Dimeric structure of the o. nova telomere end binding protein alpha subunit with bound ssdna
  1kxl		Solution structure of the cdc13 dna-binding domain in a complex with single-stranded telomeric dna (dna structure not modeled)
  1otc		The o. nova telomere end binding protein complexed with single strand dna
  1pa6		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttgagg
  1ph1		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttggggt
  1ph2		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttg
  1ph3		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttggtg
  1ph4		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttggcg
  1ph5		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttg(3dr)gg
  1ph6		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttgtgg
  1ph7		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttgigg
  1ph8		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttgcgg
  1ph9		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna ggggttttgagg
  1phj		Crystal structure of the oxytricha nova telomere end- binding protein complexed with noncognate ssdna gg(3dr) gttttgggg
  1qzg		Crystal structure of pot1 (protection of telomere)- ssdna complex
  1qzh		Crystal structure of pot1 (protection of telomere)- ssdna complex
  1s40		Solution structure of the cdc13 dna-binding domain complexed with a single-stranded telomeric dna 11-mer
  1xjv		Crystal structure of human pot1 bound to telomeric single- stranded dna (ttagggttag)
  2i0q		Crystal structure of a telomere single-strand dna-protein complex from o. nova with full-length alpha and beta telomere proteins

• Links (links to other resources describing this domain)

• PFAM	Telo_bind
  INTERPRO	IPR011564

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