Evidence map›Paper›PMID 22927644›Full record

ArticleMolecular and cellular biology2012

Replication fork collapse and genome instability in a deoxycytidylate deaminase mutant.

Arancha Sánchez, Sushma Sharma, Sophie Rozenzhak, Assen Roguev, Nevan J Krogan, Andrei Chabes, Paul Russell

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

31 citing papers in PubMed, 42 citations in OpenAlex.

  1. Cytidine and dCMP Deaminases-Current Methods of Activity Analysis.International journal of molecular sciences · 2025
    Review
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  17. Alterations in cellular metabolism triggered byProceedings of the National Academy of Sciences of the United States of America · 2017
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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

7 authors at 3 institutions in 2 countries.

Arancha SánchezDepartment of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Sushma Sharma
Sophie Rozenzhak
Assen Roguev
Nevan J Krogan
Andrei Chabes
Paul Russell
Scripps Research Institute · USUmeå University · SEUniversity of California, San Francisco · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Rewiring Therapeutic Cells: User-Controlled T Cells and Stem CellsP50GM081879 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2010 to 2017
$19.0M
Studies of the DNA damage checkpointsR01CA077325 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUSSELL, PAUL · 1998 to 2017
$7.1M
Studies of the DNA Replication CheckpointR01GM059447 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI RUSSELL, PAUL · 1999 to 2016
$6.0M
Comparative Analysis of Genetic Interaction NetworksR01GM084279 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY, KROGAN, NEVAN J · 2008 to 2017
$3.9M
Genetic Analysis of the Nucleosome and RNA Polymerase II: A Systems ApproachR01GM084448 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2008 to 2012
$2.3M
Integrating computation and genetics to quantify specificity in protein networksR01GM098101 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA, KROGAN, NEVAN J · 2011 to 2014
$1.7M
NCI NIH HHS CA77325NCI NIH HHS R01 CA077325NIAID NIH HHS P30 AI027763NIGMS NIH HHS GM081879NIGMS NIH HHS GM084279NIGMS NIH HHS GM084448NIGMS NIH HHS GM098101NIGMS NIH HHS GM59447NIGMS NIH HHS P50 GM081879NIGMS NIH HHS R01 GM059447NIGMS NIH HHS R01 GM084279NIGMS NIH HHS R01 GM084448NIGMS NIH HHS R01 GM098101
6 · The paper itself

Abstract

Ribonucleotide reductase (RNR) and deoxycytidylate deaminase (dCMP deaminase) are pivotal allosteric enzymes required to maintain adequate pools of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis and repair. Whereas RNR inhibition slows DNA replication and activates checkpoint responses, the effect of dCMP deaminase deficiency is largely unknown. Here, we report that deleting the Schizosaccharomyces pombe dcd1(+) dCMP deaminase gene (SPBC2G2.13c) increases dCTP ∼30-fold and decreases dTTP ∼4-fold. In contrast to the robust growth of a Saccharomyces cerevisiae dcd1Δ mutant, fission yeast dcd1Δ cells delay cell cycle progression in early S phase and are sensitive to multiple DNA-damaging agents, indicating impaired DNA replication and repair. DNA content profiling of dcd1Δ cells differs from an RNR-deficient mutant. Dcd1 deficiency activates genome integrity checkpoints enforced by Rad3 (ATR), Cds1 (Chk2), and Chk1 and creates critical requirements for proteins involved in recovery from replication fork collapse, including the γH2AX-binding protein Brc1 and Mus81 Holliday junction resolvase. These effects correlate with increased nuclear foci of the single-stranded DNA binding protein RPA and the homologous recombination repair protein Rad52. Moreover, Brc1 suppresses spontaneous mutagenesis in dcd1Δ cells. We propose that replication forks stall and collapse in dcd1Δ cells, burdening DNA damage and checkpoint responses to maintain genome integrity.

Indexed as

Genomic InstabilityCell CycleCheckpoint Kinase 1DCMP DeaminaseDeoxycytosine NucleotidesDNA DamageDNA HelicasesDNA RepairDNA ReplicationNucleotidyltransferasesProtein KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSchizosaccharomycesSchizosaccharomyces pombe ProteinsThymine Nucleotides2'-deoxycytidine 5'-triphosphateBrc1 protein, S pombeCheckpoint Kinase 1Chk1 protein, S pombeDCMP DeaminaseDeoxycytosine NucleotidesDNA HelicasesNucleotidyltransferasesphosphatidate cytidylyltransferaseProtein KinasesRad3 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsSchizosaccharomyces pombe Proteinsthymidine 5'-triphosphateThymine Nucleotides

Identifiers

PMID22927644
PMCPMC3486156
OpenAlexW2125437101

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.