ArticleCell death and differentiation2016
The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Review
- A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.Molecules (Basel, Switzerland) · 2023Review
- A gene dosage-dependent effect unveils NBS1 as both a haploinsufficient tumour suppressor and an essential gene for SHH-medulloblastoma.Neuropathology and applied neurobiology · 2022Article
- Replication stress defines distinct molecular subtypes across cancers.Cancer research communications · 2022Article
- Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response.International journal of molecular sciences · 2022Review
- A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.Oncogene · 2021Article
- Review
- MYC-Induced Replicative Stress: A Double-Edged Sword for Cancer Development and Treatment.International journal of molecular sciences · 2021Review
- Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?Biomolecules · 2021Review
- Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma.International journal of molecular sciences · 2020Article
- Review
- MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma.Oncotarget · 2020Article
- TheFrontiers in oncology · 2020Article
- Targeting the DNA Damage Response for the Treatment of High Risk Neuroblastoma.Frontiers in oncology · 2020Review
- SMO-M2 mutation does not support cell-autonomous Hedgehog activity in cerebellar granule cell precursors.Scientific reports · 2019Article
- DNA replication stress: oncogenes in the spotlight.Genetics and molecular biology · 2019Article
- MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors.Cell death & disease · 2018Article
- Regulation of DNA damage repair and lipid uptake by CXOncogenesis · 2018Article
- Family matters: How MYC family oncogenes impact small cell lung cancer.Cell cycle (Georgetown, Tex.) · 2017Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.
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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.