ArticleNucleic acids research2019
CtIP-BRCA1 complex and MRE11 maintain replication forks in the presence of chain terminating nucleoside analogs.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Peripheral Nerve Surgery and Chemotherapy: A Review, Index, and Decision Tree for Nerve Surgeons Considering Neurotization After Oncological Nerve Injuries.Neurosurgery practice · 2026Review
- Targeting Genome Maintenance Defects of Cancers Using Chain-Terminating Nucleoside Analogs.Cancer science · 2026Review
- A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Cancer and Radiosensitivity Syndromes: Is Impaired Nuclear ATM Kinase Activity the Primum Movens?Cancers · 2022Review
- SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination.Nucleic acids research · 2022Article
- Flap endonuclease 1 and DNA-PKcs synergistically participate in stabilizing replication fork to encounter replication stress in glioma cells.Journal of experimental & clinical cancer research : CR · 2022Article
- Mechanisms of Coronavirus Genome Stability As Potential Targets for Antiviral Drugs.Herald of the Russian Academy of Sciences · 2022Article
- DHX9-dependent recruitment of BRCA1 to RNA promotes DNA end resection in homologous recombination.Nature communications · 2021Article
- Structural basis for the coiled-coil architecture of human CtIP.Open biology · 2021Article
- Boron-containing nucleosides as tools for boron-neutron capture therapy.American journal of cancer research · 2021Review
- Genetic evidence for the involvement of mismatch repair proteins, PMS2 and MLH3, in a late step of homologous recombination.The Journal of biological chemistry · 2020Article
- The deubiquitinase USP36 Regulates DNA replication stress and confers therapeutic resistance through PrimPol stabilization.Nucleic acids research · 2020Article
- Homologous repair deficiency score for identifying breast cancers with defective DNA damage response.Scientific reports · 2020Article
- Mre11 exonuclease activity removes the chain-terminating nucleoside analog gemcitabine from the nascent strand during DNA replication.Science advances · 2020Article
- MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment.Molecular cancer · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Chain-terminating nucleoside analogs (CTNAs), which cannot be extended by DNA polymerases, are widely used as antivirals or anti-cancer agents, and can induce cell death. Processing of blocked DNA ends, like camptothecin-induced trapped-topoisomerase I, can be mediated by TDP1, BRCA1, CtIP and MRE11. Here, we investigated whether the CtIP-BRCA1 complex and MRE11 also contribute to cellular tolerance to CTNAs, including 2',3'-dideoxycytidine (ddC), cytarabine (ara-C) and zidovudine (Azidothymidine, AZT). We show that BRCA1-/-, CtIPS332A/-/- and nuclease-dead MRE11D20A/- mutants display increased sensitivity to CTNAs, accumulate more DNA damage (chromosomal breaks, γ-H2AX and neutral comets) when treated with CTNAs and exhibit significant delays in replication fork progression during exposure to CTNAs. Moreover, BRCA1-/-, CtIPS332A/-/- and nuclease-dead MRE11D20A/- mutants failed to resume DNA replication in response to CTNAs, whereas control and CtIP+/-/- cells experienced extensive recovery of DNA replication. In summary, we provide clear evidence that MRE11 and the collaborative action of BRCA1 and CtIP play a critical role in the nuclease-dependent removal of incorporated ddC from replicating genomic DNA. We propose that BRCA1-CTIP and MRE11 prepare nascent DNA ends, blocked from synthesis by CTNAs, for further repair.
Indexed as
Identifiers
What OpenQuestion holds
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.