ArticleNucleic acids research2015
Replication fork integrity and intra-S phase checkpoint suppress gene amplification.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Defects in the DNA Damage Response of Patient-derived Endometriosis Stromal Cells.bioRxiv : the preprint server for biology · 2025Article
- Tuning Methylation-Dependent Silencing Dynamics by Synthetic Modulation of CpG Density.ACS synthetic biology · 2023Article
- Cell cycle arrest and p53 prevent ON-target megabase-scale rearrangements induced by CRISPR-Cas9.Nature communications · 2023Article
- Tuning methylation-dependent silencing dynamics by synthetic modulation of CpG density.bioRxiv : the preprint server for biology · 2023Article
- Review
- PWWP2B promotes DNA end resection and homologous recombination.EMBO reports · 2022Article
- The fragility of a structurally diverse duplication block triggers recurrent genomic amplification.Nucleic acids research · 2021Article
- TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51Cell reports · 2020Article
- ATR kinase regulates its attenuation via PPM1D phosphatase recruitment to chromatin during recovery from DNA replication stress signalling.Journal of biosciences · 2018Article
- Around and beyond 53BP1 Nuclear Bodies.International journal of molecular sciences · 2017Review
- Impediment of Replication Forks by Long Non-coding RNA Provokes Chromosomal Rearrangements by Error-Prone Restart.Cell reports · 2017Article
- RecG controls DNA amplification at double-strand breaks and arrested replication forks.FEBS letters · 2017Review
- A mechanism for 1,4-Benzoquinone-induced genotoxicity.Oncotarget · 2016Article
- Reduced cohesin destabilizes high-level gene amplification by disrupting pre-replication complex bindings in human cancers with chromosomal instability.Nucleic acids research · 2016Article
- Cross talk of tyrosine kinases with the DNA damage signaling pathways.Nucleic acids research · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Gene amplification is a phenotype-causing form of chromosome instability and is initiated by DNA double-strand breaks (DSBs). Cells with mutant p53 lose G1/S checkpoint and are permissive to gene amplification. In this study we show that mammalian cells become proficient for spontaneous gene amplification when the function of the DSB repair protein complex MRN (Mre11/Rad50/Nbs1) is impaired. Cells with impaired MRN complex experienced severe replication stress and gained substrates for gene amplification during replication, as evidenced by the increase of replication-associated single-stranded breaks that were converted to DSBs most likely through replication fork reversal. Impaired MRN complex directly compromised ATM/ATR-mediated checkpoints and allowed cells to progress through cell cycle in the presence of DSBs. Such compromised intra-S phase checkpoints promoted gene amplification independently from mutant p53. Finally, cells adapted to endogenous replication stress by globally suppressing genes for DNA replication and cell cycle progression. Our results indicate that the MRN complex suppresses gene amplification by stabilizing replication forks and by securing DNA damage response to replication-associated DSBs.
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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.