ArticlePLoS genetics2012
A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Mcm5 mutation leads to silencing of Stat1-bcl2 which accelerating apoptosis of immature T lymphocytes with DNA damage.Cell death & disease · 2025Article
- Review
- 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
- Determinants of RPA megafoci localization to the nuclear periphery in response to replication stress.G3 (Bethesda, Md.) · 2022Article
- Validation of a high throughput screening assay to identify small molecules that target the eukaryotic replicative helicase.SLAS discovery : advancing life sciences R & D · 2022Article
- Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control.Biomolecules · 2022Article
- ADAR1-Mediated RNA Editing and Its Role in Cancer.Frontiers in cell and developmental biology · 2022Review
- Increased expression ofJournal of gastrointestinal oncology · 2021Article
- Active Replication Checkpoint Drives Genome Instability in Fission YeastMolecular and cellular biology · 2020Article
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- Transformation-induced stress at telomeres is counteracted through changes in the telomeric proteome including SAMHD1.Life science alliance · 2018Article
- The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Dormant origins as a built-in safeguard in eukaryotic DNA replication against genome instability and disease development.DNA repair · 2017Review
- DNA replication stress: from molecular mechanisms to human disease.Chromosoma · 2017Review
- Characterization of a Novel MMS-Sensitive Allele of Schizosaccharomyces pombe mcm4.G3 (Bethesda, Md.) · 2016Article
- Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality.Nature communications · 2015Article
- Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast.Molecular biology of the cell · 2015Article
- Managing Single-Stranded DNA during Replication Stress in Fission Yeast.Biomolecules · 2015Review
- Replication stress and cancer: it takes two to tango.Experimental cell research · 2014Review
- Biphasic response of checkpoint control proteins in hyperoxia: exposure to lower levels of oxygen induces genome maintenance genes in experimental baboon BPD.Molecular and cellular biochemistry · 2014Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H)). MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H) to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.
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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.