Saccharomyces telomeres acquire single-strand TG1–3 tails late in S phase

Wellinger, Raymund J.; Wolf, Alexander J.; Zakian, Virginia A.

doi:10.1016/0092-8674(93)90049-v

Cited by 386 publications

(394 citation statements)

References 51 publications

Supporting

Mentioning

376

Contrasting

Unclassified

Order By: Relevance

“…Therefore, results are conflicting with regard to a potential function of TRF1 in chromosome end protection. Chromosomes terminate with a singlestranded overhang of telomeric DNA (29,36). In Oxytricha nova, the telomeric end-binding protein associates with this single-stranded overhang to protect the ultimate chromosome end (18).…”

mentioning

confidence: 99%

Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function

Mattern¹,

Swiggers²,

Nigg

et al. 2004

Molecular and Cellular Biology

View full text Add to dashboard Cite

Telomeric proteins have an essential role in the regulation of the length of the telomeric DNA tract and in protection against end-to-end chromosome fusion. Telomere organization and how individual proteins are involved in different telomere functions in living cells is largely unknown. By using green fluorescent protein tagging and photobleaching, we investigated in vivo interactions of human telomeric DNA-binding proteins with telomeric DNA. Our results show that telomeric proteins interact with telomeres in a complex dynamic fashion: TRF2, which has a dual role in chromosome end protection and telomere length homeostasis, resides at telomeres in two distinct pools. One fraction (ϳ73%) has binding dynamics similar to TRF1 (residence time of ϳ44 s). Interestingly, the other fraction of TRF2 binds with similar dynamics as the putative end-protecting factor hPOT1 (residence time of ϳ11 min). Our data support a dynamic model of telomeres in which chromosome end-protection and telomere length homeostasis are governed by differential binding of telomeric proteins to telomeric DNA.

show abstract

mentioning

confidence: 99%

Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function

Mattern¹,

Swiggers²,

Nigg

et al. 2004

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…In Saccharomyces cerevisiae, terminal telomeric DNA is composed of ϳ350 base pairs of short, degenerate TG 1-3 repeats. One telomeric strand is polymerized by telomerase (Cohn and Blackburn, 1995) and forms an S-phasespecific TG 1-3 overhang (Wellinger et al, 1993(Wellinger et al, , 1996. The conventional DNA polymerase machinery is thought to synthesize the complementary C 1-3 A strand.…”

mentioning

confidence: 99%

Telomeric Protein Distributions and Remodeling Through the Cell Cycle inSaccharomyces cerevisiae

Smith

DeRisi

et al. 2003

MBoC

View full text Add to dashboard Cite

In Saccharomyces cerevisiae, telomeric DNA is protected by a nonnucleosomal protein complex, tethered by the protein Rap1. Rif and Sir proteins, which interact with Rap1p, are thought to have further interactions with conventional nucleosomic chromatin to create a repressive structure that protects the chromosome end. We showed by microarray analysis that Rif1p association with the chromosome ends extends to subtelomeric regions many kilobases internal to the terminal telomeric repeats and correlates strongly with the previously determined genomic footprints of Rap1p and the Sir2-4 proteins in these regions. Although the end-protection function of telomeres is essential for genomic stability, telomeric DNA must also be copied by the conventional DNA replication machinery and replenished by telomerase, suggesting that transient remodeling of the telomeric chromatin might result in distinct protein complexes at different stages of the cell cycle. Using chromatin immunoprecipitation, we monitored the association of Rap1p, Rif1p, Rif2p, and the protein component of telomerase, Est2p, with telomeric DNA through the cell cycle. We provide evidence for dynamic remodeling of these components at telomeres. INTRODUCTIONTelomeres are nonnucleosomal protein-DNA complexes that prevent uncontrolled fusion, degradation, recombination, and elongation of chromosome ends (Muller, 1938;McClintock, 1941;Wright et al., 1992;Sandell and Zakian, 1993;Hande et al., 1999;Smith and Blackburn, 1999;Hackett et al., 2001). In Saccharomyces cerevisiae, terminal telomeric DNA is composed of ϳ350 base pairs of short, degenerate TG 1-3 repeats. One telomeric strand is polymerized by telomerase (Cohn and Blackburn, 1995) and forms an S-phasespecific TG 1-3 overhang (Wellinger et al., 1993(Wellinger et al., , 1996. The conventional DNA polymerase machinery is thought to synthesize the complementary C 1-3 A strand. Duplex telomeric DNA repeats are bound by the sequence-specific binding protein Rap1p, which recruits proteins Rif1p and Rif2p as well as Sir3p and Sir4p via its C-terminal domain (Moretti et al., 1994;Moazed and Johnson, 1996;Moretti and Shore, 2001).Telomeric regions in yeast also contain subtelomeric X-elements, which have only moderate homology to each other and are present at all chromosome ends, and the highly homologous YЈ elements located distal to the X elements (Chan and Tye, 1983) on about half of all chromosome ends. YЈ elements fall into 5.2-and 6.7-kb size classes (Louis and Haber, 1990;Louis and Haber, 1992), encode a helicase (Yamada et al., 1998), and are bounded by short (Ͻ150-base pair) tracts of internal telomeric TG 1-3 sequence DNA. Because YЈ elements often occur in tandem arrays of two to four repeats, these TG 1-3 tracts are found internal to the chromosome ends at distances depending upon the size class and number of YЈ elements present.The Rap1p, Ku, and Sir2-4 proteins are cross-linkable to DNA as far in as 3-15 kb from the chromosome end, consistent with their simultaneous binding to TG [1][2][3] repeat DNA ...

show abstract

“…Nos résultats récents suggèrent que, comme chez les ciliés, les télomères de levure possèdent une extension de 12-15 bases durant la plus grande partie du cycle cellulaire (données non publiées), à l'exception de la fin de la phase S où ils acquièrent, de façon transitoire, des extensions G-riches de plus de 30 nucléo-tides [11]. Ces longues extensions sont présentes sur tous les télomères après réplication de l'ADN, c'est-à-dire aux deux extrémités de chaque chromosome [12].…”

Section: Levures: Petites Variations Sur Le Thèmeunclassified

Structure terminale des chromosomes : le « capuchon télomérique »

LeBel

Wellinger²

2004

Med Sci (Paris)

Self Cite

View full text Add to dashboard Cite

maintenant établi dans la communauté scientifique. Ce que l'on connaissait de la machinerie de réplication conventionnelle, incapable de synthétiser l'extrémité de molécules d'ADN linéaires comme les chromosomes eucaryotes, laissait supposer que les télomères devaient subir des pertes de leurs séquences terminales au fil des cycles de réplication. Chez les humains, on observe effectivement un raccourcissement des chromosomes dans la plupart des cellules somatiques au fil des années, et l'hypothèse selon laquelle les télomères joueraient un rôle déterminant dans la sénescence cellulaire a été proposée. Cependant, il existe une enzyme spécifique, la télomérase, d'abord identifiée chez le cilié Tetrahymena en 1985, qui peut prévenir ce raccourcissement naturel des chromosomes en ajoutant des répétitions télomériques à leurs extrémités [3]. Cette enzyme est absente de la plupart des cellules humaines somatiques normales. En revanche, chez l'homme, elle est présente et activée dans les cellules germinales, dans la plupart des lignées de cellules transformées et dans 90% des cellules cancéreuses primaires [4]. Ce lien entre activation de la télomérase et carcinogenèse a suscité un grand enthousiasme dans la communauté scientifique, suggérant que des thérapies anticancé-Les études du généticien H.J. Muller sur les chromosomes de la drosophile ont donné naissance au concept de télomère en 1938. H.J. Muller observa que des délétions ou des inversions induites par irradiation aux rayons X de l'ensemble du génome étaient quasiment indétectables dans les régions terminales des chromosomes [1]. Il en conclut que les extrémités des chromosomes, qu'il nomma télomères, devaient posséder une structure particulière capable de stabiliser les chromosomes. À la même époque, B. McClintock démontra que des chromosomes du maïs ayant subi des cassures double brin étaient capables de fusionner entre eux, contrairement à leurs extrémités qui demeuraient stables [2]. Le modèle le plus récent suggère que les télomères agissent comme des structures qui protègent les chromosomes d'éventuelles fusions de leurs extrémités, de l'intervention de la machinerie de réparation (qui les considère-rait comme des cassures double brin) et de la dégrada-tion par des exonucléases. Ces structures protectrices, que nous proposons d'appeler « capuchons télomé-riques», sont constituées par l'association d'ADN télo-mérique et de protéines spécifiques. Ce nouveau concept de capuchon protecteur des chromosomes est

show abstract

Saccharomyces telomeres acquire single-strand TG1–3 tails late in S phase

Cited by 386 publications

References 51 publications

Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function

Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function

Telomeric Protein Distributions and Remodeling Through the Cell Cycle inSaccharomyces cerevisiae

Structure terminale des chromosomes : le « capuchon télomérique »

Contact Info

Product

Resources

About