ArticleMolecular biology of the cell2008
A mutant allele of MRE11 found in mismatch repair-deficient tumor cells suppresses the cellular response to DNA replication fork stress in a dominant negative manner.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
- Trial
- MRE11 Deficiency Occurs in a Small Group of Cancers from Various Different Tumor Entities.Diagnostics (Basel, Switzerland) · 2026Article
- Recruitment of Mre11 to recombination sites during meiosis.Nature communications · 2026Article
- Cell Type Specific Suppression of Hyper-Recombination by Human RAD18 Is Linked to Proliferating Cell Nuclear Antigen K164 Ubiquitination.Biomolecules · 2025Article
- MRE11A: a novel negative regulator of human DNA mismatch repair.Cellular & molecular biology letters · 2024Article
- An activity-based functional test for identifying homologous recombination deficiencies across cancer types in real time.Cell reports. Medicine · 2023Article
- Loss of TDP-43 function contributes to genomic instability in amyotrophic lateral sclerosis.Frontiers in neuroscience · 2023Article
- Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer.Cells · 2022Review
- Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy.Clinical science (London, England : 1979) · 2022Article
- NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations.Scientific reports · 2021Article
- Review
- Review
- MRNIP is a replication fork protection factor.Science advances · 2020Article
- Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC).DNA repair · 2020Review
- Decoding non-random mutational signatures at Cas9 targeted sites.Nucleic acids research · 2018Article
- Review
- Transcriptional activation of p21Oncotarget · 2018Article
- AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11.Oncogene · 2018Article
- Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.Nucleic acids research · 2018Review
- Cancer Cells with Alternative Lengthening of Telomeres Do Not Display a General Hypersensitivity to ATR Inhibition.Frontiers in oncology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interaction of ataxia-telangiectasia mutated (ATM) and the Mre11/Rad50/Nbs1 (MRN) complex is critical for the response of cells to DNA double-strand breaks; however, little is known of the role of these proteins in response to DNA replication stress. Here, we report a mutant allele of MRE11 found in a colon cancer cell line that sensitizes cells to agents causing replication fork stress. The mutant Mre11 weakly interacts with Rad50 relative to wild type and shows little affinity for Nbs1. The mutant protein lacks 3'-5' exonuclease activity as a result of loss of part of the conserved nuclease domain; however, it retains binding affinity for single-stranded DNA (ssDNA), double-stranded DNA with a 3' single-strand overhang, and fork-like structures containing ssDNA regions. In cells, the mutant protein shows a time- and dose-dependent accumulation in chromatin after thymidine treatment that corresponds with increased recruitment and hyperphosphorylation of replication protein A. ATM autophosphorylation, Mre11 foci, and thymidine-induced homologous recombination are suppressed in cells expressing the mutant allele. Together, our results suggest that the mutant Mre11 suppresses the cellular response to replication stress by binding to ssDNA regions at disrupted forks and impeding replication restart in a dominant negative manner.
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