ArticlePLoS genetics2010
Incremental genetic perturbations to MCM2-7 expression and subcellular distribution reveal exquisite sensitivity of mice to DNA replication stress.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed, 90 citations in OpenAlex.
- Chronic replication stress-mediated genomic instability disrupts placenta development in mice.PLoS genetics · 2026Article
- Expression and prognostic value of MCM2 in type B thymomas.BMC cancer · 2025Article
- Biophysical investigation of the molecular interaction between minichromosome maintenance protein 6 and Bloom syndrome helicase.The FEBS journal · 2025Article
- Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells.Cancer research communications · 2025Article
- Identification of MCM2-Interacting Proteins Associated with Replication Initiation Using APEX2-Based Proximity Labeling Technology.International journal of molecular sciences · 2025Article
- The widely used Ucp1-Cre transgene elicits complex developmental and metabolic phenotypes.Nature communications · 2025Article
- ANXA4 restricts HBV replication by inhibiting autophagic degradation of MCM2 in chronic hepatitis B.BMC medicine · 2024Article
- The widely usedbioRxiv : the preprint server for biology · 2023Article
- The importance of nuclear RAGE-Mcm2 axis in diabetes or cancer-associated replication stress.Nucleic acids research · 2023Article
- Familial Glucocorticoid Deficiency: the changing landscape of an eponymous syndrome.Frontiers in endocrinology · 2023Review
- MCM2 in human cancer: functions, mechanisms, and clinical significance.Molecular medicine (Cambridge, Mass.) · 2022Review
- Mcm2 hypomorph leads to acute leukemia or hematopoietic stem cell failure, dependent on genetic context.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Mammalian Resilience Revealed by a Comparison of Human Diseases and Mouse Models Associated With DNA Helicase Deficiencies.Frontiers in molecular biosciences · 2022Review
- MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer.Frontiers in genetics · 2022Article
- TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress.Nucleic acids research · 2021Article
- San1 deficiency leads to cardiomyopathy due to excessive R-loop-associated DNA damage and cardiomyocyte hypoplasia.Biochimica et biophysica acta. Molecular basis of disease · 2021Observational
- Human NK cell deficiency as a result of biallelic mutations in MCM10.The Journal of clinical investigation · 2020Article
- MCMs in Cancer: Prognostic Potential and Mechanisms.Analytical cellular pathology (Amsterdam) · 2020Review
- Down-regulation of CK2α correlates with decreased expression levels of DNA replication minichromosome maintenance protein complex (MCM) genes.Scientific reports · 2019Article
- KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells.PLoS biology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations causing replication stress can lead to genomic instability (GIN). In vitro studies have shown that drastic depletion of the MCM2-7 DNA replication licensing factors, which form the replicative helicase, can cause GIN and cell proliferation defects that are exacerbated under conditions of replication stress. To explore the effects of incrementally attenuated replication licensing in whole animals, we generated and analyzed the phenotypes of mice that were hemizygous for Mcm2, 3, 4, 6, and 7 null alleles, combinations thereof, and also in conjunction with the hypomorphic Mcm4(Chaos3) cancer susceptibility allele. Mcm4(Chaos3/Chaos3) embryonic fibroblasts have ∼40% reduction in all MCM proteins, coincident with reduced Mcm2-7 mRNA. Further genetic reductions of Mcm2, 6, or 7 in this background caused various phenotypes including synthetic lethality, growth retardation, decreased cellular proliferation, GIN, and early onset cancer. Remarkably, heterozygosity for Mcm3 rescued many of these defects. Consistent with a role in MCM nuclear export possessed by the yeast Mcm3 ortholog, the phenotypic rescues correlated with increased chromatin-bound MCMs, and also higher levels of nuclear MCM2 during S phase. The genetic, molecular and phenotypic data demonstrate that relatively minor quantitative alterations of MCM expression, homeostasis or subcellular distribution can have diverse and serious consequences upon development and confer cancer susceptibility. The results support the notion that the normally high levels of MCMs in cells are needed not only for activating the basal set of replication origins, but also "backup" origins that are recruited in times of replication stress to ensure complete replication of the genome.
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.