Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length

The yeast protein RAP1, initially described as a transcriptional regulator, binds in vitro to sequences found in a number of seemingly unrelated genomic loci. These include the silencers at the transcriptionally repressed mating-type genes, the promoters of many genes important for cell growth, and the poly[(cytosine)1-3 adenine] [poly(C1-3A)] repeats of telomeres. Because RAP1 binds in vitro to the poly(C1-3A) repeats of telomeres, it has been suggested that RAP1 may be involved in telomere function in vivo. In order to test this hypothesis, the telomere tract lengths of yeast strains that contained conditionally lethal (ts) rap1 mutations were analyzed. Several rap1ts alleles reduced telomere length in a temperature-dependent manner. In addition, plasmids that contain small, synthetic telomeres with intact or mutant RAP1 binding sites were tested for their ability to function as substrates for poly(C1-3A) addition in vivo. Mutations in the RAP1 binding sites reduced the efficiency of the addition reaction.

[1]  G. Morin The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats , 1989, Cell.

[2]  C. Cantor,et al.  Isolation and characterization of a human telomere. , 1989, Nucleic acids research.

[3]  M. Olson,et al.  Cloning human telomeric DNA fragments into Saccharomyces cerevisiae using a yeast-artificial-chromosome vector. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Brand,et al.  RAP-1 factor is necessary for DNA loop formation in vitro at the silent mating type locus HML , 1989, Cell.

[5]  E. Blackburn,et al.  Telomere terminal transferase activity from Euplotes crassus adds large numbers of TTTTGGGG repeats onto telomeric primers , 1989, Molecular and cellular biology.

[6]  J. Szostak,et al.  A mutant with a defect in telomere elongation leads to senescence in yeast , 1989, Cell.

[7]  W. Brown Molecular cloning of human telomeres in yeast , 1989, Nature.

[8]  S. Cross,et al.  Cloning of human telomeres by complementation in yeast , 1989, Nature.

[9]  E. Blackburn,et al.  A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis , 1989, Nature.

[10]  V A Zakian,et al.  Structure and function of telomeres. , 1989, Annual review of genetics.

[11]  R. Kornberg,et al.  Connections between transcriptional activators, silencers, and telomeres as revealed by functional analysis of a yeast DNA-binding protein , 1988, Molecular and cellular biology.

[12]  A. Murray,et al.  Characterization of two telomeric DNA processing reactions in Saccharomyces cerevisiae , 1988, Molecular and Cellular Biology.

[13]  M. Grunstein,et al.  Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast , 1988, Cell.

[14]  Kim Nasmyth,et al.  Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements , 1987, Cell.

[15]  D. Shore,et al.  Identification of silencer binding proteins from yeast: possible roles in SIR control and DNA replication , 1987, The EMBO journal.

[16]  A. Murray,et al.  Construction and behavior of circularly permuted and telocentric chromosomes in Saccharomyces cerevisiae , 1986, Molecular and cellular biology.

[17]  B. Tye,et al.  Identification of a telomere-binding activity from yeast. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Astell,et al.  The Saccharomyces cerevisiae chromosome III left telomere has a type X, but not a type Y', ARS region , 1986, Molecular and cellular biology.

[19]  T. Petes,et al.  Identification of yeast mutants with altered telomere structure. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  E. Blackburn,et al.  Chromatin structure of the telomeric region and 3'-nontranscribed spacer of Tetrahymena ribosomal RNA genes. , 1986, The Journal of biological chemistry.

[21]  J. Buhler,et al.  A general upstream binding factor for genes of the yeast translational apparatus. , 1985, The EMBO journal.

[22]  Carol W. Greider,et al.  Identification of a specific telomere terminal transferase activity in tetrahymena extracts , 1985, Cell.

[23]  L. Hartwell,et al.  CDC17: An essential gene that prevents telomere elongation in yeast , 1985, Cell.

[24]  R. Walmsley,et al.  Genetic control of chromosome length in yeast. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Szostak,et al.  Transfer of yeast telomeres to linear plasmids by recombination , 1984, Cell.

[26]  T. Cech,et al.  Chromatin structure of the molecular ends of oxytricha macronuclear DNA: phased nucleosomes and a telomeric complex , 1984, Cell.

[27]  T. Petes,et al.  Unusual DNA sequences associated with the ends of yeast chromosomes , 1984, Nature.

[28]  Jack W. Szostak,et al.  DNA sequences of telomeres maintained in yeast , 1984, Nature.

[29]  E. Blackburn Telomeres: Do the ends justify the means? , 1984, Cell.

[30]  V. Zakian,et al.  Elaboration of telomeres in yeast: recognition and modification of termini from Oxytricha macronuclear DNA. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Szostak,et al.  Is there left-handed DNA at the ends of yeast chromosomes? , 1983, Nature.

[32]  J. Strathern,et al.  Homothallic switching of yeast mating type cassettes is initiated by a double-stranded cut in the MAT locus , 1982, Cell.

[33]  K. Nasmyth The regulation of yeast mating-type chromatin structure by SIR: An action at a distance affecting both transcription and transposition , 1982, Cell.

[34]  J. Strathern,et al.  A position-effect control for gene transposition: State of expression of yeast mating-type genes affects their ability to switch , 1981, Cell.

[35]  L. Hartwell,et al.  Macromolecule Synthesis in Temperature-sensitive Mutants of Yeast , 1967, Journal of bacteriology.