Evidence map›Paper›PMID 21852961›Full record

ArticlePLoS genetics2011

Ku must load directly onto the chromosome end in order to mediate its telomeric functions.

Christopher R Lopez, Albert Ribes-Zamora, Sandra M Indiviglio, Christopher L Williams, Svasti Haricharan, Alison A Bertuch

Abstract read
In one paragraph

Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Article
  2. Article
  3. The Multifaceted Roles of Ku70/80.International journal of molecular sciences · 2021
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Consider the workhorse: Nonhomologous end-joining in budding yeast.Biochemistry and cell biology = Biochimie et biologie cellulaire · 2016
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Genome-wide studies of telomere biology in budding yeast.Microbial cell (Graz, Austria) · 2014
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Christopher R LopezDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America. abertuch@bcm.edu
Albert Ribes-Zamora
Sandra M Indiviglio
Christopher L Williams
Svasti Haricharan
Alison A Bertuch

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9M
Initiative for Maximizing Student Development (IMSD) ProgramR25GM056929 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI PEREIRA, FRED A · 1998 to 2023
$12.4M
Research Education and Career Horizons ProgramK12GM084897 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI SIFERS, RICHARD NORMAN, SLAUGHTER, GAYLE · 2008 to 2016
$8.3M
The Roles of the Ku Heterodimer in Yeast Telomere FunctionR01GM077509 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI BERTUCH, ALISON A · 2007 to 2018
$3.0M
Molecular Determinants that Govern Ku's Association with TelomeresF31AG034764 · NIA · BAYLOR COLLEGE OF MEDICINE · PI INDIVIGLIO, SANDRA MELANIE LOUISE · 2010 to 2012
$79k
NCI NIH HHS P30 CA125123NIA NIH HHS F31 AG034764NIGMS NIH HHS 3R01GM077509-01A2S1NIGMS NIH HHS 3R01GM077509-03S1NIGMS NIH HHS 5R01GM077509-04NIGMS NIH HHS K12 GM084897NIGMS NIH HHS R01 GM077509NIGMS NIH HHS R25 GM056929
6 · The paper itself

Abstract

The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where it impacts several aspects of telomere structure and function. Although Ku avidly binds DNA ends via a preformed channel, its ability to associate with telomeres via this mechanism could be challenged by factors known to bind directly to the chromosome terminus. This has led to uncertainty as to whether Ku itself binds directly to telomeric ends and whether end association is crucial for Ku's telomeric functions. To address these questions, we constructed DNA end binding-defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that were predicted to contact DNA. These mutants continued to associate with their known telomere-related partners, such as Sir4, a factor required for telomeric silencing, and TLC1, the RNA component of telomerase. Despite these interactions, we found that the Ku mutants had markedly reduced association with telomeric chromatin and null-like deficiencies for telomere end protection, length regulation, and silencing functions. In contrast to Ku null strains, the DNA end binding defective Ku mutants resulted in increased, rather than markedly decreased, imprecise end-joining proficiency at an induced double-strand break. This result further supports that it was the specific loss of Ku's telomere end binding that resulted in telomeric defects rather than global loss of Ku's functions. The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance.

Indexed as

Saccharomyces cerevisiaeChromosomes, FungalDNA-Binding ProteinsElectrophoretic Mobility Shift AssayImmunoprecipitationMutagenesis, Site-DirectedMutation, MissenseProtein BindingRecombination, GeneticSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeTelomeraseTelomereDNA-Binding Proteinshigh affinity DNA-binding factor, S cerevisiaeSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSIR4 protein, S cerevisiaeTelomerase

Identifiers

PMID21852961
PMCPMC3154960

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.