Pot1, the Putative Telomere End-Binding Protein in Fission Yeast and Humans

Telomere proteins from ciliated protozoa bind to the single-stranded G-rich DNA extensions at the ends of macronuclear chromosomes. We have now identified homologous proteins in fission yeast and in humans. These Pot1 (protection oftelomeres) proteins each bind the G-rich strand of their own telomeric repeat sequence, consistent with a direct role in protecting chromosome ends. Deletion of the fission yeastpot1 + gene has an immediate effect on chromosome stability, causing rapid loss of telomeric DNA and chromosome circularization. It now appears that the protein that caps the ends of chromosomes is widely dispersed throughout the eukaryotic kingdom.

[1]  T. Cech,et al.  Oxytricha telomere-binding protein: separable DNA-binding and dimerization domains of the alpha-subunit. , 1993, Genes & development.

[2]  J. Griffith,et al.  Mammalian Telomeres End in a Large Duplex Loop , 1999, Cell.

[3]  S. R. Vorel,et al.  Relapse to Cocaine-Seeking After Hippocampal Theta Burst Stimulation , 2001, Science.

[4]  D. Prescott,et al.  All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3' terminus. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Langmore,et al.  Long G Tails at Both Ends of Human Chromosomes Suggest a C Strand Degradation Mechanism for Telomere Shortening , 1997, Cell.

[6]  S. Dupuis,et al.  Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase , 1998, Nature Genetics.

[7]  R. Wellinger,et al.  Saccharomyces telomeres acquire single-strand TG1–3 tails late in S phase , 1993, Cell.

[8]  C. Price,et al.  Euplotes crassus has genes encoding telomere-binding proteins and telomere-binding protein homologs. , 1992, Nucleic acids research.

[9]  H. Cooke,et al.  hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. , 1992, Nucleic acids research.

[10]  P. Baumann,et al.  Protection of telomeres by the Ku protein in fission yeast. , 2000, Molecular biology of the cell.

[11]  C B Harley,et al.  Telomerase catalytic subunit homologs from fission yeast and human. , 1997, Science.

[12]  J. Shay,et al.  Normal human chromosomes have long G-rich telomeric overhangs at one end. , 1997, Genes & development.

[13]  T. Cech,et al.  Two modes of survival of fission yeast without telomerase. , 1998, Science.

[14]  L. Hartwell,et al.  Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint , 1995, Molecular and cellular biology.

[15]  N. Maizels,et al.  In Vitro Properties of the Conserved Mammalian Protein hnRNP D Suggest a Role in Telomere Maintenance , 2000, Molecular and Cellular Biology.

[16]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[17]  D. Bowtell,et al.  Isolation of a candidate human telomerase catalytic subunit gene, which reveals complex splicing patterns in different cell types. , 1997, Human molecular genetics.

[18]  C. Dobell.  The Biology of the Protozoa , 1926, Nature.

[19]  R. Weinberg,et al.  hEST2, the Putative Human Telomerase Catalytic Subunit Gene, Is Up-Regulated in Tumor Cells and during Immortalization , 1997, Cell.

[20]  G. Dreyfuss,et al.  Nuclear proteins that bind the pre-mRNA 3' splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n , 1993, Molecular and cellular biology.

[21]  A. Murzin.  OB(oligonucleotide/oligosaccharide binding)‐fold: common structural and functional solution for non‐homologous sequences. , 1993, The EMBO journal.

[22]  R. Wellinger,et al.  The terminal DNA structure of mammalian chromosomes , 1997, The EMBO journal.

[23]  V. Lundblad,et al.  Cdc13 Delivers Separate Complexes to the Telomere for End Protection and Replication , 2001, Cell.

[24]  D. Gottschling,et al.  Telomere proteins: Specific recognition and protection of the natural termini of Oxytricha macronuclear DNA , 1986, Cell.

[25]  T. Cech,et al.  Molecular cloning of telomere-binding protein genes from Stylonychia mytilis. , 1991, Nucleic acids research.

[26]  A. Matsuura,et al.  Circular chromosome formation in a fission yeast mutant defective in two ATM homologues , 1998, Nature Genetics.

[27]  C. Cantor,et al.  Construction of a Not I restriction map of the fission yeast Schizosaccharomyces pombe genome. , 1989, Nucleic acids research.

[28]  T. Alber,et al.  Modulation of transcription factor Ets-1 DNA binding: DNA-induced unfolding of an alpha helix. , 1995, Science.

[29]  M. Horvath,et al.  Crystal Structure of the Oxytricha nova Telomere End Binding Protein Complexed with Single Strand DNA , 1998, Cell.

[30]  T. Cech,et al.  Modulation of telomerase activity by telomere DNA-binding proteins in Oxytricha. , 1998, Genes & development.

[31]  T. Cech,et al.  Oxytricha telomere-binding protein: DNA-dependent dimerization of the alpha and beta subunits. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Evans,et al.  Est1 and Cdc13 as comediators of telomerase access. , 1999, Science.

[33]  T. Cech,et al.  Cloning and expression of genes for the Oxytricha telomere-binding protein: Specific subunit interactions in the telomeric complex , 1991, Cell.

[34]  D. Prescott,et al.  Evolution of the scrambled germline gene encoding α-telomere binding protein in three hypotrichous ciliates , 1998, Chromosoma.