ArticlePLoS genetics2016
Chronic DNA Replication Stress Reduces Replicative Lifespan of Cells by TRP53-Dependent, microRNA-Assisted MCM2-7 Downregulation.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
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- Quantitative profiling of adaptation to cyclin E overproduction.Life science alliance · 2022Article
- HREM, RNAseq and Cell Cycle Analyses Reveal the Role of the G2/M-Regulatory Protein, WEE1, on the Survivability of Chicken Embryos during Diapause.Biomedicines · 2022Article
- Chromatin loading of MCM hexamers is associated with di-/tri-methylation of histone H4K20 toward S phase entry.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
- Exosomes and Micro-RNAs in Aging Process.Biomedicines · 2021Review
- Targeting OGG1 arrests cancer cell proliferation by inducing replication stress.Nucleic acids research · 2020Article
- Proteomic and Phosphoproteomic Maps of Lung Squamous Cell Carcinoma From Chinese Patients.Frontiers in oncology · 2020Article
- Jie-Du-Hua-Yu Granules Promote Liver Regeneration in Rat Models of Acute Liver Failure: miRNA-mRNA Expression Analysis.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Replication Stress and Consequential Instability of the Genome and Epigenome.Molecules (Basel, Switzerland) · 2019Review
- Involvement of Dual Strands ofInternational journal of molecular sciences · 2019Article
- Article
- The Protective Role of Dormant Origins in Response to Replicative Stress.International journal of molecular sciences · 2018Review
- P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance.Nature communications · 2017Article
- Dormant origins as a built-in safeguard in eukaryotic DNA replication against genome instability and disease development.DNA repair · 2017Review
- Review
- Too much to handle - how gaining chromosomes destabilizes the genome.Cell cycle (Georgetown, Tex.) · 2016Review
- The Chromatin Remodeling Component Arid1a Is a Suppressor of Spontaneous Mammary Tumors in Mice.Genetics · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Circumstances that compromise efficient DNA replication, such as disruptions to replication fork progression, cause a state known as DNA replication stress (RS). Whereas normally proliferating cells experience low levels of RS, excessive RS from intrinsic or extrinsic sources can trigger cell cycle arrest and senescence. Here, we report that a key driver of RS-induced senescence is active downregulation of the Minichromosome Maintenance 2-7 (MCM2-7) factors that are essential for replication origin licensing and which constitute the replicative helicase core. Proliferating cells produce high levels of MCM2-7 that enable formation of dormant origins that can be activated in response to acute, experimentally-induced RS. However, little is known about how physiological RS levels impact MCM2-7 regulation. We found that chronic exposure of primary mouse embryonic fibroblasts (MEFs) to either genetically-encoded or environmentally-induced RS triggered gradual MCM2-7 repression, followed by inhibition of replication and senescence that could be accelerated by MCM hemizygosity. The MCM2-7 reduction in response to RS is TRP53-dependent, and involves a group of Trp53-dependent miRNAs, including the miR-34 family, that repress MCM expression in replication-stressed cells before they undergo terminal cell cycle arrest. miR-34 ablation partially rescued MCM2-7 downregulation and genomic instability in mice with endogenous RS. Together, these data demonstrate that active MCM2-7 repression is a physiologically important mechanism for RS-induced cell cycle arrest and genome maintenance on an organismal level.
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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.