Evidence map›Paper›PMID 23785298›Full record

ArticlePLoS genetics2013

Fragile DNA motifs trigger mutagenesis at distant chromosomal loci in saccharomyces cerevisiae.

Natalie Saini, Yu Zhang, Yuri Nishida, Ziwei Sheng, Shilpa Choudhury, Piotr Mieczkowski, Kirill S Lobachev

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

31 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
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  8. Review
  9. Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022
    Article
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  14. Review
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  18. GC content elevates mutation and recombination rates in the yeastProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  19. Review
  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

7 authors at 2 institutions in 1 country.

Natalie SainiSchool of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
Yu Zhang
Yuri Nishida
Ziwei Sheng
Shilpa Choudhury
Piotr Mieczkowski
Kirill S Lobachev
Georgia Institute of Technology · USUNC Lineberger Comprehensive Cancer Center

Funding

Mechanism and consequences of GAA repeat-mediated chromosomal fragility in yeastR01GM082950 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI LOBACHEV, KIRILL S · 2008 to 2011
$1.2M
NIGMS NIH HHS R01 GM082950NIGMS NIH HHS R01GM082950
6 · The paper itself

Abstract

DNA sequences capable of adopting non-canonical secondary structures have been associated with gross-chromosomal rearrangements in humans and model organisms. Previously, we have shown that long inverted repeats that form hairpin and cruciform structures and triplex-forming GAA/TTC repeats induce the formation of double-strand breaks which trigger genome instability in yeast. In this study, we demonstrate that breakage at both inverted repeats and GAA/TTC repeats is augmented by defects in DNA replication. Increased fragility is associated with increased mutation levels in the reporter genes located as far as 8 kb from both sides of the repeats. The increase in mutations was dependent on the presence of inverted or GAA/TTC repeats and activity of the translesion polymerase Polζ. Mutagenesis induced by inverted repeats also required Sae2 which opens hairpin-capped breaks and initiates end resection. The amount of breakage at the repeats is an important determinant of mutations as a perfect palindromic sequence with inherently increased fragility was also found to elevate mutation rates even in replication-proficient strains. We hypothesize that the underlying mechanism for mutagenesis induced by fragile motifs involves the formation of long single-stranded regions in the broken chromosome, invasion of the undamaged sister chromatid for repair, and faulty DNA synthesis employing Polζ. These data demonstrate that repeat-mediated breaks pose a dual threat to eukaryotic genome integrity by inducing chromosomal aberrations as well as mutations in flanking genes.

Indexed as

Genomic InstabilityChromosome AberrationsChromosomesDNA Breaks, Double-StrandedInverted Repeat SequencesMutagenesisNucleic Acid ConformationNucleotide MotifsSaccharomyces cerevisiaeTrinucleotide Repeats

Identifiers

PMID23785298
PMCPMC3681665
OpenAlexW2024002114

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.