ArticlePloS one2009
c-Myc accelerates S-phase and requires WRN to avoid replication stress.
Article in PloS one, 2009. 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
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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.
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Who cites it
59 citing papers in PubMed, 76 citations in OpenAlex.
- Exploiting replication stress for synthetic lethality in MYC-driven cancers.American journal of cancer research · 2025Review
- Review
- CDK12 controls transcription at damaged genes and prevents MYC-induced transcription-replication conflicts.Nature communications · 2024Article
- XPO1 Enables Adaptive Regulation of mRNA Export Required for Genotoxic Stress Tolerance in Cancer Cells.Cancer research · 2024Article
- [The role of the response to DNA damage in granulomatous diseases].Zeitschrift fur Rheumatologie · 2022Article
- Distinct signaling signatures drive compensatory proliferation via S-phase acceleration.PLoS genetics · 2022Article
- Cellular senescence in neuroblastoma.British journal of cancer · 2022Review
- Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response.International journal of molecular sciences · 2022Review
- MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.Journal of hematology & oncology · 2021Review
- A novel inhibitor L755507 efficiently blocks c-Myc-MAX heterodimerization and induces apoptosis in cancer cells.The Journal of biological chemistry · 2021Article
- MYC-Induced Replicative Stress: A Double-Edged Sword for Cancer Development and Treatment.International journal of molecular sciences · 2021Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- Synthetic Lethal Interactions of RECQ Helicases.Trends in cancer · 2021Review
- Dihydrocapsaicin Inhibits Cell Proliferation and Metastasis in MelanomaFrontiers in oncology · 2021Article
- Article
- Review
- DNA replication stress: oncogenes in the spotlight.Genetics and molecular biology · 2019Article
- CDK12: an emerging therapeutic target for cancer.Journal of clinical pathology · 2018Review
- Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells.Molecular and cellular biochemistry · 2018Article
- Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas.Cell systems · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
c-Myc interacts with components of the pre-replication complex and directly regulates DNA replication [1]. However the consequences of this novel c-Myc function on cell cycle dynamics and replication-associated damage are unknown. Here, we show that c-Myc overexpression in primary human fibroblasts markedly accelerates S-phase while c-Myc deficient fibroblasts exhibit a prolonged S-phase. We also show that the Werner DNA helicase protein (WRN) plays a critical role in supporting c-Myc-driven S-phase, as depletion of WRN in c-Myc overexpressing cells increases DNA damage specifically at sites of DNA synthesis. This excess DNA damage activates a "replication stress" pathway involving ATR, CHK1, CHK2, and p53, leading to rapid senescence of WRN deficient c-Myc overexpressing cells. Indeed, depletion of p53 rescues this senescence response. We propose that WRN functions to repair abnormal replication structures caused by the acceleration of DNA replication by c-Myc. This work provides an additional mechanistic explanation for c-Myc-induced DNA damage and senescence, and reveals a vulnerability of c-Myc overexpressing cells that could potentially be exploited in cancer therapy.
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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.