ArticleCell cycle (Georgetown, Tex.)2013
INK4a/ARF limits the expansion of cells suffering from replication stress.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- Article
- IGF-binding protein 2 is a candidate target of therapeutic potential in cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Chronic DNA Replication Stress Reduces Replicative Lifespan of Cells by TRP53-Dependent, microRNA-Assisted MCM2-7 Downregulation.PLoS genetics · 2016Article
- Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells.Nature communications · 2015Article
- Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.Genes & development · 2015Article
- Suppression of the DHX9 helicase induces premature senescence in human diploid fibroblasts in a p53-dependent manner.The Journal of biological chemistry · 2014Article
- Regulation and roles of Cdc7 kinase under replication stress.Cell cycle (Georgetown, Tex.) · 2014Review
- MKK7 and ARF: new players in the DNA damage response scenery.Cell cycle (Georgetown, Tex.) · 2014Article
- Rapamycin induces pluripotent genes associated with avoidance of replicative senescence.Cell cycle (Georgetown, Tex.) · 2013Article
- The Mre11 complex suppresses oncogene-driven breast tumorigenesis and metastasis.Molecular cell · 2013Article
- INK4a/ARF-dependent senescence upon persistent replication stress.Cell cycle (Georgetown, Tex.) · 2013Article
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Replication stress (RS) is a source of DNA damage that has been linked to cancer and aging, which is suppressed by the ATR kinase. In mice, reduced ATR levels in a model of the ATR-Seckel syndrome lead to RS and accelerated aging. Similarly, ATR-Seckel embryonic fibroblasts (MEF) accumulate RS and undergo cellular senescence. We previously showed that senescence of ATR-Seckel MEF cannot be rescued by p53-deletion. Here, we show that the genetic ablation of the INK4a/Arf locus fully rescues senescence on ATR mutant MEF, but also that induced by other conditions that generate RS such as low doses of hydroxyurea or ATR inhibitors. In addition, we show that a persistent exposure to RS leads to increased levels of INK4a/Arf products, revealing that INK4a/ARF behaves as a bona fide RS checkpoint. Our data reveal an unknown role for INK4a/ARF in limiting the expansion of cells suffering from persistent replication stress, linking this well-known tumor suppressor to the maintenance of genomic integrity.
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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.