Evidence map›Paper›PMID 24001775›Full record

ArticleMolecular and cellular biology2013

Inactivation of Uaf1 causes defective homologous recombination and early embryonic lethality in mice.

Eunmi Park, Jung Min Kim, Benjamin Primack, David M Weinstock, Lisa A Moreau, Kalindi Parmar, Alan D D'Andrea

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

26 citing papers in PubMed, 41 citations in OpenAlex.

  1. Double jeopardy: howFrontiers in cell and developmental biology · 2026
    Review
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  4. Nutrients · 2021
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  8. DNA repair fidelity in stem cell maintenance, health, and disease.Biochimica et biophysica acta. Molecular basis of disease · 2020
    Review
  9. Review
  10. Article
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  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. The Fanconi anaemia pathway: new players and new functions.Nature reviews. Molecular cell biology · 2016
    Review
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.

Eunmi ParkDepartment of Radiation Oncology.
Jung Min Kim
Benjamin Primack
David M Weinstock
Lisa A Moreau
Kalindi Parmar
Alan D D'Andrea
Harvard University · USDana-Farber Cancer Institute · US

Funding

Xenograft CoreP01HL048546 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI FLEMING, WILLIAM H · 1994 to 2020
$36.4M
CORE--ZEBRAFISHP30DK049216 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1999 to 2015
$14.3M
MOLECULAR PATHOGENESIS OF FANCONI ANEMIAR01HL052725 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI ALAN D. D'ANDREA · 1994 to 2026
$5.9M
STRUCTURE AND FUNCTION OF THE ERYTHROPOIETIN RECEPTORR01DK043889 · NIDDK · DANA-FARBER CANCER INSTITUTE · PI D'ANDREA, ALAN D. · 1992 to 2014
$5.3M
NHLBI NIH HHS P01 HL048546NHLBI NIH HHS P01HL048546NHLBI NIH HHS R01 HL052725NHLBI NIH HHS R01HL52725NIDDK NIH HHS 5P30 DK49216-19NIDDK NIH HHS P30 DK049216NIDDK NIH HHS R01 DK043889NIDDK NIH HHS R01DK43889
6 · The paper itself

Abstract

The deubiquitinating enzyme heterodimeric complex USP1-UAF1 regulates the Fanconi anemia (FA) DNA repair pathway. Absence of this complex leads to increased cellular levels of ubiquitinated FANCD2 (FANCD2-Ub) and ubiquitinated PCNA (PCNA-Ub). Mice deficient in the catalytic subunit of the complex, USP1, exhibit an FA-like phenotype and have a cellular deficiency in homologous-recombination (HR) repair. Here, we have characterized mice deficient in the UAF1 subunit. Uaf1(+/-) mice were small at birth and exhibited reduced fertility, thus resembling Usp1(-/-) mice. Unexpectedly, homozygous Uaf1(-/-) embryos died at embryonic day 7.5 (E7.5). These mutant embryos were small and developmentally retarded. As expected, Uaf1 deficiency in mice led to increased levels of cellular Fancd2-Ub and Pcna-Ub. Uaf1(+/-) murine embryonic fibroblasts (MEFs) exhibited profound chromosome instability, genotoxin hypersensitivity, and a significant defect in homologous-recombination repair. Moreover, Uaf1(-/-) mouse embryonic stem cells (mESCs) showed chromosome instability, genotoxin hypersensitivity, and impaired Fancd2 focus assembly. Similar to USP1 knockdown, UAF1 knockdown in tumor cells caused suppression of tumor growth in vivo. Taken together, our data demonstrate the important regulatory role of the USP1-UAF1 complex in HR repair through its regulation of the FANCD2-Ub and PCNA-Ub cellular pools.

Indexed as

Gene DeletionHomologous RecombinationAnimalsCarcinogenesisCells, CulturedChromosomal InstabilityDNA RepairEmbryo LossEmbryonic Stem CellsFanconi Anemia Complementation Group D2 ProteinFemaleFibroblastsHomozygoteHumansInfertilityMaleFanconi Anemia Complementation Group D2 ProteinMutagensNuclear ProteinsProliferating Cell Nuclear Antigen

Identifiers

PMID24001775
PMCPMC3838189
OpenAlexW2119085876

What OpenQuestion holds

Textmetadata
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.