Evidence map›Paper›PMID 39445827›Full record

ArticleNucleic acids research2024

Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks.

Qilin Long, Kamal Ajit, Katerina Sedova, Vojtech Haluza, Richard Stefl, Sadat Dokaneheifard, Felipe Beckedorff, Monica G Valencia, Marek Sebesta, Ramin Shiekhattar and 1 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
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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

11 authors.

Qilin LongSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Kamal AjitSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Katerina SedovaCEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic.
Vojtech HaluzaCEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic.
Richard SteflCEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic.ORCID 0000-0003-0558-5952
Sadat DokaneheifardDepartment of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA.
Felipe BeckedorffDepartment of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA.ORCID 0000-0001-6735-6851
Monica G ValenciaDepartment of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA.
Marek SebestaCEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic.ORCID 0000-0001-9546-4921
Ramin ShiekhattarDepartment of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA.
Monika GullerovaSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.ORCID 0000-0002-4512-2779

Funding

Elucidation of Integrator's FunctionR01GM078455 · NIGMS · WISTAR INSTITUTE · PI SHIEKHATTAR, RAMIN · 2010 to 2025
$5.1M
Cancer Research UK BVR01170EPA Trust Fund BVR01670European Research Council 649030Grant Agency of the Czech Republic 21-10464MLee Placito FundMinistry of Education CZ.02.01.01/00/22_008/0004575NIGMS NIH HHS R01 GM078455Sylvester Comprehensive Cancer Center R01GM078455University of Oxford
6 · The paper itself

Abstract

DNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regulatory mechanisms governing the transcription cycle at DSBs are not well understood. Here, we show that Integrator complex subunit 6 (INTS6) associates with the heterotrimeric sensor of ssDNA (SOSS1) complex (comprising INTS3, INIP and hSSB1) to form the tetrameric SOSS1 complex. INTS6 binds to DNA:RNA hybrids and promotes Protein Phosphatase 2A (PP2A) recruitment to DSBs, facilitating the dephosphorylation of RNAPII. Furthermore, INTS6 prevents the accumulation of damage-associated RNA transcripts (DARTs) and the stabilization of DNA:RNA hybrids at DSB sites. INTS6 interacts with and promotes the recruitment of senataxin (SETX) to DSBs, facilitating the resolution of DNA:RNA hybrids/R-loops. Our results underscore the significance of the tetrameric SOSS1 complex in the autoregulation of DNA:RNA hybrids and efficient DNA repair.

Indexed as

DNADNA Breaks, Double-StrandedDNA RepairRNARNA Polymerase IIDNA-Binding ProteinsDNA HelicasesHomeostasisHumansPhosphorylationProtein Phosphatase 2R-Loop StructuresRNA HelicasesDNADNA-Binding ProteinsDNA HelicasesProtein Phosphatase 2RNARNA HelicasesRNA Polymerase II

Identifiers

PMID39445827
PMCPMC11602137

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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.