Evidence map›Paper›PMID 22279048›Full record

ArticleGenes & development2012

R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants.

Peter C Stirling, Yujia A Chan, Sean W Minaker, Maria J Aristizabal, Irene Barrett, Payal Sipahimalani, Michael S Kobor, Philip Hieter

Abstract read
In one paragraph

Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.

0numbers the graph read from it
0cells of the map it votes in
154citing 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

154 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025
    Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Chromosomal R-loops: who R they?Biologia futura · 2024
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Article

94 more citing papers are in PubMed but not listed here.

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

8 authors.

Peter C StirlingMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Yujia A Chan
Sean W Minaker
Maria J Aristizabal
Irene Barrett
Payal Sipahimalani
Michael S Kobor
Philip Hieter

Funding

Functional Determinants of Chromosome SegregationR01CA158162 · NCI · UNIVERSITY OF BRITISH COLUMBIA · PI HIETER, PHILIP A. · 2012 to 2016
$1.1M
CIHRNCI NIH HHS R01 CA158162
6 · The paper itself

Abstract

Genome instability via RNA:DNA hybrid-mediated R loops has been observed in mutants involved in various aspects of transcription and RNA processing. The prevalence of this mechanism among essential chromosome instability (CIN) genes remains unclear. In a secondary screen for increased Rad52 foci in CIN mutants, representing ∼25% of essential genes, we identified seven essential subunits of the mRNA cleavage and polyadenylation (mCP) machinery. Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops. In parallel, we directly detected increased RNA:DNA hybrid formation in mCP mutants and demonstrated that CIN is suppressed by expression of the R-loop-degrading enzyme RNaseH. To investigate the conservation of CIN in mCP mutants, we focused on FIP1L1, the human ortholog of yeast FIP1, a conserved mCP component that is part of an oncogenic fusion in eosinophilic leukemia. We found that truncation fusions of yeast FIP1 analogous to those in cancer cause loss of function and that siRNA knockdown of FIP1L1 in human cells increases DNA damage and chromosome breakage. Our findings illuminate how mCP maintains genome integrity by suppressing R-loop formation and suggest that this function may be relevant to certain human cancers.

Indexed as

MutationChromosome Fragile SitesGenomic InstabilityHCT116 CellsHumansmRNA Cleavage and Polyadenylation FactorsOpen Reading FramesRad52 DNA Repair and Recombination ProteinRecombinant Fusion ProteinsReplication OriginSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsFIP1L1 protein, humanFIP1 protein, S cerevisiaemRNA Cleavage and Polyadenylation FactorsRad52 DNA Repair and Recombination ProteinRecombinant Fusion ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID22279048
PMCPMC3273840

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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.