Evidence map›Paper›PMID 30091972›Full record

ArticlePLoS genetics2018

Single-strand annealing between inverted DNA repeats: Pathway choice, participating proteins, and genome destabilizing consequences.

Sreejith Ramakrishnan, Zachary Kockler, Robert Evans, Brandon D Downing, Anna Malkova

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

  1. Assessment and Mitigation of CRISPR-Cas9-Induced Nontargeted Translocations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  2. Article
  3. POLD3 as Controller of Replicative DNA Repair.International journal of molecular sciences · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Break-induced replication mechanisms in yeast and mammals.Current opinion in genetics & development · 2021
    Review
  15. Article
  16. Single-Strand Annealing in Cancer.International journal of molecular sciences · 2021
    Review
  17. Review
  18. 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

5 authors at 2 institutions in 1 country.

Sreejith RamakrishnanDepartment of Biology, University of Iowa, Iowa City, IA, United States of America.ORCID 0000-0002-0514-9694
Zachary KocklerDepartment of Biology, University of Iowa, Iowa City, IA, United States of America.ORCID 0000-0001-7828-3520
Robert EvansIndiana University Purdue University Indianapolis, Indianapolis, IN, United States of America.ORCID 0000-0002-8985-3979
Brandon D DowningIndiana University Purdue University Indianapolis, Indianapolis, IN, United States of America.ORCID 0000-0001-8666-9263
Anna MalkovaDepartment of Biology, University of Iowa, Iowa City, IA, United States of America.ORCID 0000-0002-3880-1781
University of Iowa · USUniversity of Indianapolis · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
Double strand break repair maelstrom: causes, mechanisms and genome destabilizing consequencesR35GM127006 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Anna L Malkova · 2018 to 2026
$3.8M
NIGMS NIH HHS R35 GM127006
6 · The paper itself

Abstract

Double strand DNA breaks (DSBs) are dangerous events that can result from various causes including environmental assaults or the collapse of DNA replication. While the efficient and precise repair of DSBs is essential for cell survival, faulty repair can lead to genetic instability, making the choice of DSB repair an important step. Here we report that inverted DNA repeats (IRs) placed near a DSB can channel its repair from an accurate pathway that leads to gene conversion to instead a break-induced replication (BIR) pathway that leads to genetic instabilities. The effect of IRs is explained by their ability to form unusual DNA structures when present in ssDNA that is formed by DSB resection. We demonstrate that IRs can form two types of unusual DNA structures, and the choice between these structures depends on the length of the spacer separating IRs. In particular, IRs separated by a long (1-kb) spacer are predominantly involved in inter-molecular single-strand annealing (SSA) leading to the formation of inverted dimers; IRs separated by a short (12-bp) spacer participate in intra-molecular SSA, leading to the formation of fold-back (FB) structures. Both of these structures interfere with an accurate DSB repair by gene conversion and channel DSB repair into BIR, which promotes genomic destabilization. We also report that different protein complexes participate in the processing of FBs containing short (12-bp) versus long (1-kb) ssDNA loops. Specifically, FBs with short loops are processed by the MRX-Sae2 complex, whereas the Rad1-Rad10 complex is responsible for the processing of long loops. Overall, our studies uncover the mechanisms of genomic destabilization resulting from re-routing DSB repair into unusual pathways by IRs. Given the high abundance of IRs in the human genome, our findings may contribute to the understanding of IR-mediated genomic destabilization associated with human disease.

Indexed as

DNA Breaks, Double-StrandedDNA Repeat ExpansionDNA, Single-StrandedBase SequenceDNA RepairDNA ReplicationGene ConversionGene DeletionGene RearrangementMolecular StructureRecombination, GeneticSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDNA, Single-StrandedSaccharomyces cerevisiae Proteins

Identifiers

PMID30091972
PMCPMC6103520
OpenAlexW2885733696

What OpenQuestion holds

Textmetadata
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.