title: Duplication and functional specialization of the telomere-capping protein Cdc13 in Candida species.
abstract: The budding yeast G-tail binding complex CST (Cdc13-Stn1-Ten1) is crucial for both telomere protection and replication. Previous studies revealed a family of Cdc13 orthologues (Cdc13A) in Candida species that are unusually small but are nevertheless responsible for G-tail binding and the regulation of telomere lengths and structures. Here we report the identification and characterization of a second family of Cdc13-like proteins in the Candida clade, named Cdc13B. Phylogenetic analysis and sequence alignment indicate that Cdc13B probably arose through gene duplication prior to Candida speciation. Like Cdc13A, Cdc13B appears to be essential. Deleting one copy each of the CDC13A and CDC13B genes caused a synergistic effect on aberrant telomere elongation and t-circle accumulation, suggesting that the two paralogues mediate overlapping and nonredundant functions in telomere regulation. Interestingly, Cdc13B utilizes its C-terminal OB-fold domain (OB4) to mediate self-association and binding to Cdc13A. Moreover, the stability of the heterodimer is evidently greater than that of either homodimer. Both the Cdc13 A/A homodimer and A/B heterodimer, but not the B/B homodimer, recognized the telomere G-tail repeat with high affinity and sequence specificity. Our results reveal novel evolutionary elaborations of the G-tail-binding protein in Saccharomycotina yeast, suggesting a drastic remodeling of CDC13 that entails gene duplication, fusion, and functional specialization. The repeated and independent duplication of G-tail-binding proteins such as Cdc13 and Pot1 hints at the evolutionary advantage of having multiple G-tail-binding proteins.
authors: From the Department of Microbiology and Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, New York, New York 10065.
authors: Neal F
authors: NF
authors: Lue
authors: Jamie
authors: J
authors: Chan
mesh_terms: D001483:Base Sequence; D002175:Candida / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000378:metabolism; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020440:Gene Duplication; D005990:Glycerol / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D034501:Telomere-Binding Proteins; D005990:Glycerol
keywords: CST; Cdc13; Chromosomes; Chromosomes/Non-histone Chromosomal Proteins; DNA-Protein Interaction; Dimerization; OB Fold; Telomerase; Telomeres
references: Mol Cell Biol. 2012 Jan;32(1):186-98
references: 22025677
references: Cell. 2008 Mar 7;132(5):745-57
references: 18329362
references: Nat Struct Mol Biol. 2007 Mar;14(3):208-14
references: 17293872
references: Mol Cell. 2000 May;5(5):865-76
references: 10882122
references: J Bacteriol. 2000 Oct;182(20):5730-6
references: 11004171
references: Science. 2009 Nov 13;326(5955):948-52
references: 19965504
references: PLoS Genet. 2008 Oct;4(10):e1000236
references: 18949040
references: EMBO J. 1993 Feb;12(2):607-16
references: 8440250
references: Cell. 2006 Jul 14;126(1):63-77
references: 16839877
references: Genes Dev. 2009 Dec 15;23(24):2900-14
references: 20008938
references: EMBO J. 2009 Apr 8;28(7):799-809
references: 19214183
references: Genetics. 1993 Jul;134(3):717-28
references: 8349105
references: Structure. 2013 Jan 8;21(1):109-120
references: 23177925
references: Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20362-9
references: 21969561
references: PLoS Genet. 2013;9(1):e1003145
references: 23300477
references: Biochemistry. 2011 Jul 26;50(29):6289-91
references: 21668015
references: Mol Cell Biol. 2010 Nov;30(22):5325-34
references: 20837709
references: Cell. 2001 Feb 9;104(3):387-96
references: 11239396
references: Mol Cell. 2010 Sep 10;39(5):665-76
references: 20832719
references: Mol Cell Biol. 2010 Mar;30(5):1254-68
references: 20008550
references: Nat Cell Biol. 2006 Jul;8(7):748-55
references: 16767082
references: Trends Biochem Sci. 2010 Jan;35(1):8-17
references: 19846312
references: EMBO J. 2008 Sep 3;27(17):2328-39
references: 19172739
references: Mol Cell Biol. 2005 Sep;25(17):7725-33
references: 16107718
references: Nat Rev Mol Cell Biol. 2010 Mar;11(3):171-81
references: 20125188
references: Yeast. 2001 Jun 30;18(9):859-64
references: 11427968
references: J Bacteriol. 1999 Mar;181(6):1868-74
references: 10074081
references: Cell Res. 2011 Feb;21(2):258-74
references: 20877309
references: J Mol Biol. 2004 Apr 23;338(2):241-55
references: 15066429
references: Nat Biotechnol. 1999 Oct;17(10):1030-2
references: 10504710