CDC13/YDL220C Summary Help

Standard Name CDC13 1, 2
Systematic Name YDL220C
Alias EST4 3
Feature Type ORF, Verified
Description Single stranded DNA-binding protein found at TG1-3 telomere G-tails; key roles in regulation of telomerase, telomere end protection, conventional telomere replication; regulates telomere replication through recruitment of specific sub-complexes, essential function is telomere capping; forms homodimer via N-terminus; disruption of dimerization leads to short telomeres; autophagy and proteasome are involved in Cdc13p degradation; differentially phosphorylated through cell cycle (4, 5, 6, 7 and see Summary Paragraph)
Name Description Cell Division Cycle 8
Chromosomal Location
ChrIV:65018 to 62244 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: -122 cM
Gene Ontology Annotations All CDC13 GO evidence and references
  View Computational GO annotations for CDC13
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Resources
Classical genetics
conditional
null
overexpression
reduction of function
unspecified
Large-scale survey
null
overexpression
reduction of function
repressible
Resources
964 total interaction(s) for 579 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 7
  • Affinity Capture-Western: 18
  • Biochemical Activity: 19
  • Co-crystal Structure: 3
  • Co-localization: 1
  • Co-purification: 1
  • Reconstituted Complex: 15
  • Two-hybrid: 30

Genetic Interactions
  • Dosage Growth Defect: 6
  • Dosage Lethality: 3
  • Dosage Rescue: 14
  • Negative Genetic: 96
  • Phenotypic Enhancement: 26
  • Phenotypic Suppression: 34
  • Positive Genetic: 182
  • Synthetic Growth Defect: 160
  • Synthetic Lethality: 42
  • Synthetic Rescue: 307

Resources
Expression Summary
histogram
Resources
Length (a.a.) 924
Molecular Weight (Da) 104,903
Isoelectric Point (pI) 6.55
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:65018 to 62244 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: -122 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2775 65018..62244 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002379
SUMMARY PARAGRAPH for CDC13

Cdc13p is a multi-functional, telomere-binding protein that plays a role in telomere replication, length maintenance, end protection and telomerase regulation (4). CDC13/EST4 is one of five genes required for telomerase activity in vivo. EST1, EST2, TLC1 and EST3 are the other four genes. Mutations in any of these five genes leads to progressive telomere shortening, the so-called ever shorter telomeres (EST) phenotype and eventually to cell death; however, a complete deletion of CDC13 is inviable. CDC13 is the only essential gene among the EST genes (9, 10, 11, 12, 13 and references therein).

The N-terminal region of Cdc13p is crucial for the protein's activity due to its various interactions with different binding proteins (14). The telomere capping function is mediated through its interaction with Stn1p and Ten1p, essential proteins required for telomere length regulation (15, 16, 17). Cdc13p plays a role in telomere replication through its interactions with the Pol1p catalytic subunit of DNA polymerase alpha, and an essential subunit of telomerase, Est1p (18). Cdc13p and Est1p also recruit and activate the telomere-bound Est2p catalytic subunit of telomerase for its replication (19). The telomerase recruitment step is regulated by the yeast ku heterodimer (Yku70p-Yku80p), and Stn1p which impart positive and negative control on the Cdc13p-Est1p interaction (13, 20). Cdc13p is regulated by the phosphorylation of the SQ/TQ motif in the telomerase recruitment domain by the checkpoint kinases, Mec1p and Tel1p (21). Mutation in Cdc13p results in abnormal uncapped telomeres with long exposed G-strands leading to activation of the RAD9 DNA damage pathway, cell cycle arrest at the G2/M phase and cell death (1, 22, 23, 24, 14).

In humans, telomere length is linked to aging and cancer: in human germline cells telomeres are long, whereas in cells of somatic tissues, telomerase activity is absent and the telomeres are short. Upon sufficient shortening, the somatic cells stop dividing and become senescent. Inappropriate telomerase activity is detected in most malignant tumors, and the genes required for telomerase activity are potential targets for cancer therapy (25, 10).

Human orthologs for four of the telomerase subunits are known. Est2p, the telomerase reverse transcriptase catalytic enzyme, is similar to TERT (OMIM), TLC1, the template RNA is similar to TERC/hTR (OMIM), while Cdc13p shares sequence similarity with human POT1 (OMIM) (26, 11). There are three Est1p like proteins in humans, although only hEST1A and hEST1B have been shown to be associated with the telomerase (27). A human ortholog for EST3 hasn't been identified. Mutations in TERT (OMIM) and TERC/hTR (OMIM) cause short telomeres and congenital aplastic anemia (OMIM, 26).

Last updated: 2007-06-27 Contact SGD

References cited on this page View Complete Literature Guide for CDC13
1) Garvik B, et al.  (1995) Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol Cell Biol 15(11):6128-38
2) Garvik, B. and Hartwell, L.  (1989) Personal Communication, Mortimer Map Edition 10
3) Lendvay TS, et al.  (1996) Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics 144(4):1399-412
4) Lustig AJ  (2001) Cdc13 subcomplexes regulate multiple telomere functions. Nat Struct Biol 8(4):297-9
5) Baek GH, et al.  (2012) The Cdc48 protein and its cofactor Vms1 are involved in Cdc13 protein degradation. J Biol Chem 287(32):26788-95
6) Wu Y, et al.  (2013) Novel Phosphorylation Sites in the S. cerevisiae Cdc13 Protein Reveal New Targets for Telomere Length Regulation. J Proteome Res 12(1):316-27
7) Lewis KA, et al.  (2014) The tenacious recognition of yeast telomere sequence by Cdc13 is fully exerted by a single OB-fold domain. Nucleic Acids Res 42(1):475-84
8) Hartwell LH, et al.  (1970) Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc Natl Acad Sci U S A 66(2):352-9
9) Zakian VA  (1996) Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30:141-72
10) Lowell JE and Pillus L  (1998) Telomere tales: chromatin, telomerase and telomere function in Saccharomyces cerevisiae. Cell Mol Life Sci 54(1):32-49
11) Smogorzewska A and de Lange T  (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177-208
12) Taggart AK and Zakian VA  (2003) Telomerase: what are the Est proteins doing? Curr Opin Cell Biol 15(3):275-80
13) Dubrana K, et al.  (2001) Turning telomeres off and on. Curr Opin Cell Biol 13(3):281-9
14) Hsu CL, et al.  (2004) Interaction of Saccharomyces Cdc13p with Pol1p, Imp4p, Sir4p and Zds2p is involved in telomere replication, telomere maintenance and cell growth control. Nucleic Acids Res 32(2):511-21
15) Petreaca RC, et al.  (2006) Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p. Nat Cell Biol 8(7):748-55
16) Grandin N, et al.  (1997) Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes Dev 11(4):512-27
17) Grandin N, et al.  (2001) Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13. EMBO J 20(5):1173-83
18) Qi H and Zakian VA  (2000) The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev 14(14):1777-88
19) Taggart AK, et al.  (2002) Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 297(5583):1023-6
20) Grandin N, et al.  (2000) Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Mol Cell Biol 20(22):8397-408
21) Tseng SF, et al.  (2006) The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res 34(21):6327-36
22) Lin JJ and Zakian VA  (1996) The Saccharomyces CDC13 protein is a single-strand TG1-3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo. Proc Natl Acad Sci U S A 93(24):13760-5
23) Pennock E, et al.  (2001) Cdc13 delivers separate complexes to the telomere for end protection and replication. Cell 104(3):387-96
24) Nugent CI, et al.  (1996) Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science 274(5285):249-52
25) Barinaga M  (1997) The telomerase picture fills in. Science 276(5312):528-9
26) Yamaguchi H, et al.  (2005) Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med 352(14):1413-24
27) Lundblad V  (2003) Telomere replication: an Est fest. Curr Biol 13(11):R439-41