Evidence map›Paper›PMID 39025073›Full record

ArticleMolecular cell2024

The splicing factor CCAR1 regulates the Fanconi anemia/BRCA pathway.

Naoya Harada, Shuhei Asada, Lige Jiang, Huy Nguyen, Lisa Moreau, Ryan J Marina, Karen Adelman, Divya R Iyer, Alan D D'Andrea

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Disruption of Microhomology-mediated End-joining in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025
    Article
  5. [Advancements in CRISPR-Cas9 for Fanconi anemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Naoya HaradaDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Shuhei AsadaDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Lige JiangDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Huy NguyenDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Lisa MoreauDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Ryan J MarinaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Karen AdelmanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Divya R IyerDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: divyar_iyer@dfci.harvard.edu.
Alan D D'AndreaDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: alan_dandrea@dfci.harvard.edu.

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
MOLECULAR PATHOGENESIS OF FANCONI ANEMIAR01HL052725 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI ALAN D. D'ANDREA · 1994 to 2026
$5.9M
NCI NIH HHS P30 CA006516NHLBI NIH HHS R01 HL052725
6 · The paper itself

Abstract

The twenty-three Fanconi anemia (FA) proteins cooperate in the FA/BRCA pathway to repair DNA interstrand cross-links (ICLs). The cell division cycle and apoptosis regulator 1 (CCAR1) protein is also a regulator of ICL repair, though its possible function in the FA/BRCA pathway remains unknown. Here, we demonstrate that CCAR1 plays a unique upstream role in the FA/BRCA pathway and is required for FANCA protein expression in human cells. Interestingly, CCAR1 co-immunoprecipitates with FANCA pre-mRNA and is required for FANCA mRNA processing. Loss of CCAR1 results in retention of a poison exon in the FANCA transcript, thereby leading to reduced FANCA protein expression. A unique domain of CCAR1, the EF hand domain, is required for interaction with the U2AF heterodimer of the spliceosome and for excision of the poison exon. Taken together, CCAR1 is a splicing modulator required for normal splicing of the FANCA mRNA and other mRNAs involved in various cellular pathways.

Indexed as

Apoptosis Regulatory ProteinsCell Cycle ProteinsFanconi AnemiaFanconi Anemia Complementation Group A ProteinRNA SplicingSplicing Factor U2AFBRCA1 ProteinBRCA2 ProteinDNA RepairEndodeoxyribonucleasesExonsHEK293 CellsHeLa CellsHumansProtein BindingRNA, MessengerApoptosis Regulatory ProteinsBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanCCAR1 protein, humanCell Cycle ProteinsEndodeoxyribonucleasesFANCA protein, humanFanconi Anemia Complementation Group A ProteinRBBP8 protein, humanRNA, MessengerRNA PrecursorsSplicing Factor U2AFU2AF1 protein, humanalternative splicingCCAR1DNA repairEF handFANCAFanconi anemiapoison exonU2AF1/2

Identifiers

PMID39025073
PMCPMC11321822

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.