ArticlePLoS genetics2015
Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Titin Is Present in the Elastic Tethers That Connect Separating Anaphase Chromosomes in Crane-Fly Spermatocytes.Cytoskeleton (Hoboken, N.J.) · 2026Article
- A hybrid RNA-based reporter assay for robust quantification of cytidine deaminase activity.Nucleic acids research · 2026Article
- Integrative multi-omics framework for causal gene discovery in Long COVID.PLoS computational biology · 2025Article
- Cytidine and dCMP Deaminases-Current Methods of Activity Analysis.International journal of molecular sciences · 2025Review
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Cytidine Deaminase Resolves Replicative Stress and Protects Pancreatic Cancer from DNA-Targeting Drugs.Cancer research · 2024Article
- Structural evidence for elastic tethers connecting separating chromosomes in crane-fly spermatocytes.Life science alliance · 2023Article
- Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA.Nucleic acids research · 2023Article
- Targeting theFrontiers in cell and developmental biology · 2023Review
- Linking DNA repair and cell cycle progression through serine ADP-ribosylation of histones.Nature communications · 2022Article
- Breaking the aging epigenetic barrier.Frontiers in cell and developmental biology · 2022Review
- Regulation of mitotic chromosome architecture and resolution of ultrafine anaphase bridges by PICH.Cell cycle (Georgetown, Tex.) · 2021Article
- The role of phosphorylation in the elasticity of the tethers that connect telomeres of separating anaphase chromosomes.Nucleus (Austin, Tex.) · 2020Article
- A decrease in NAMPT activity impairs basal PARP-1 activity in cytidine deaminase deficient-cells, independently of NADScientific reports · 2020Article
- Topoisomerase IIα prevents ultrafine anaphase bridges by two mechanisms.Open biology · 2020Article
- PARP and PARG inhibitors in cancer treatment.Genes & development · 2020Review
- The Emerging Role of Cytidine Deaminase in Human Diseases: A New Opportunity for Therapy?Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Quantitation of deoxynucleoside triphosphates by click reactions.Scientific reports · 2020Article
- Elastic Tethers Between Separating Anaphase Chromosomes Regulate the Poleward Speeds of the Attached Chromosomes in Crane-Fly Spermatocytes.Frontiers in molecular biosciences · 2020Article
- Mitotic functions of poly(ADP-ribose) polymerases.Biochemical pharmacology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA) deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS), a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.