Evidence map›Paper›PMID 25830313›Full record

ArticlePLoS genetics2015

Genome-destabilizing effects associated with top1 loss or accumulation of top1 cleavage complexes in yeast.

Sabrina L Andersen, Roketa S Sloan, Thomas D Petes, Sue Jinks-Robertson

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
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

19 citing papers in PubMed, 28 citations in OpenAlex.

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  16. Review
  17. Article
  18. Topoisomerases and the regulation of neural function.Nature reviews. Neuroscience · 2016
    Review
  19. 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

4 authors at 1 institution in 1 country.

Sabrina L AndersenDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Roketa S SloanDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Thomas D PetesDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Sue Jinks-RobertsonDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Duke University · US

Funding

Genetics Training Grant-Year 26T32GM007754 · NIGMS · DUKE UNIVERSITY · PI HAASE, STEVEN B · 1985 to 2019
$8.3M
RECOMBINATION IN YEASTR01GM024110 · NIGMS · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI PETES, THOMAS · 1985 to 2015
$6.1M
INSTABILITY OF SIMPLE REPETITIVE DNA SEQUENCES IN YEASTR01GM052319 · NIGMS · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI PETES, THOMAS · 1995 to 2015
$4.9M
CANCER BIOLOGY TRAINING GRANTT32CA059365 · NCI · DUKE UNIVERSITY · PI WANG, XIAO-FAN · 1993 to 2014
$4.4M
REGULATION OF MITOTIC RECOMBINATION IN YEASTR01GM038464 · NIGMS · EMORY UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1992 to 2015
$3.6M
Topoisomerase 1 and mutagenesis in yeastR01GM101690 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 2012 to 2015
$1.3M
Topoisomerase-Associated Genome InstabilityF32GM100618 · NIGMS · DUKE UNIVERSITY · PI COTE, SABRINA · 2012 to 2013
$101k
RECOMBINATION BETWEEN REPEATED SEQUENCE IN YEASTR29GM038464 · NIGMS · EMORY UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1987 to 1991
–
NCI NIH HHS CA059365NCI NIH HHS T32 CA059365NIGMS NIH HHS F32 GM100618NIGMS NIH HHS GM024110NIGMS NIH HHS GM038464NIGMS NIH HHS GM052319NIGMS NIH HHS GM100618NIGMS NIH HHS GM101690NIGMS NIH HHS R01 GM024110NIGMS NIH HHS R01 GM038464NIGMS NIH HHS R01 GM052319NIGMS NIH HHS R01 GM101690NIGMS NIH HHS T32 GM007754
6 · The paper itself

Abstract

Topoisomerase 1 (Top1), a Type IB topoisomerase, functions to relieve transcription- and replication-associated torsional stress in DNA. We investigated the effects of Top1 on genome stability in Saccharomyces cerevisiae using two different assays. First, a sectoring assay that detects loss of heterozygosity (LOH) on a specific chromosome was used to measure reciprocal crossover (RCO) rates. Features of individual RCO events were then molecularly characterized using chromosome-specific microarrays. In the second assay, cells were sub-cultured for 250 generations and LOH was examined genome-wide using microarrays. Though loss of Top1 did not destabilize single-copy genomic regions, RCO events were more complex than in a wild-type strain. In contrast to the stability of single-copy regions, sub-culturing experiments revealed that top1 mutants had greatly elevated levels of instability within the tandemly-repeated ribosomal RNA genes (in agreement with previous results). An intermediate in the enzymatic reaction catalyzed by Top1 is the covalent attachment of Top1 to the cleaved DNA. The resulting Top1 cleavage complex (Top1cc) is usually transient but can be stabilized by the drug camptothecin (CPT) or by the top1-T722A allele. We found that increased levels of the Top1cc resulted in a five- to ten-fold increase in RCOs and greatly increased instability within the rDNA and CUP1 tandem arrays. A detailed analysis of the events in strains with elevated levels of Top1cc suggests that recombinogenic DNA lesions are introduced during or after DNA synthesis. These results have important implications for understanding the effects of CPT as a chemotherapeutic agent.

Indexed as

Genomic InstabilityCamptothecinCrossing Over, GeneticDNA Topoisomerases, Type IGenome, FungalMutationRNA, RibosomalSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTopoisomerase I InhibitorsCamptothecinDNA Topoisomerases, Type IRNA, RibosomalSaccharomyces cerevisiae ProteinsTopoisomerase I Inhibitors

Identifiers

PMID25830313
PMCPMC4382028
OpenAlexW1979831207

What OpenQuestion holds

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Registered trials

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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.