ArticlePLoS genetics2016
A Checkpoint-Related Function of the MCM Replicative Helicase Is Required to Avert Accumulation of RNA:DNA Hybrids during S-phase and Ensuing DSBs during G2/M.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 35 citations in OpenAlex.
- C1ORF112 drives lung adenocarcinoma progression through e2f8-mediated transcriptional activation.Journal of thoracic disease · 2026Article
- An improved cytological assay for R-loop detection in Saccharomyces cerevisiae utilizing a catalytically inactive RNase H.G3 (Bethesda, Md.) · 2025Article
- A new insight into the impact of copy number variations on cell cycle deregulation of luminal-type breast cancer.Oncology reviews · 2025Review
- Review
- MCM8 interacts with DDX5 to promote R-loop resolution.The EMBO journal · 2024Article
- R-loop and diseases: the cell cycle matters.Molecular cancer · 2024Review
- Integrative analysis and prediction of human R-loop binding proteins.G3 (Bethesda, Md.) · 2022Article
- Validation of a high throughput screening assay to identify small molecules that target the eukaryotic replicative helicase.SLAS discovery : advancing life sciences R & D · 2022Article
- Transcription-Replication Collisions-A Series of Unfortunate Events.Biomolecules · 2021Review
- Gene Co-Expression Analysis of HumanBiology · 2021Article
- MCM10 compensates for Myc-induced DNA replication stress in breast cancer stem-like cells.Cancer science · 2021Article
- MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression at transcription-replication conflicts.Nature communications · 2019Article
- Transcription-mediated replication hindrance: a major driver of genome instability.Genes & development · 2019Review
- A High-Throughput Assay for DNA Replication Inhibitors Based upon Multivariate Analysis of Yeast Growth Kinetics.SLAS discovery : advancing life sciences R & D · 2019Article
- R-loop formation during S phase is restricted by PrimPol-mediated repriming.The EMBO journal · 2019Article
- Resting cells rely on the DNA helicase component MCM2 to build cilia.Nucleic acids research · 2019Article
- Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place.Cancer discovery · 2018Review
- Review
- When DNA Topology Turns Deadly - RNA Polymerases Dig in Their R-Loops to Stand Their Ground: New Positive and Negative (Super)Twists in the Replication-Transcription Conflict.Trends in genetics : TIG · 2018Review
- RECQ-like helicases Sgs1 and BLM regulate R-loop-associated genome instability.The Journal of cell biology · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Mcm2-7 complex is the catalytic core of the eukaryotic replicative helicase. Here, we identify a new role for this complex in maintaining genome integrity. Using both genetic and cytological approaches, we find that a specific mcm allele (mcm2DENQ) causes elevated genome instability that correlates with the appearance of numerous DNA-damage associated foci of γH2AX and Rad52. We further find that the triggering events for this genome instability are elevated levels of RNA:DNA hybrids and an altered DNA topological state, as over-expression of either RNaseH (an enzyme specific for degradation of RNA in RNA:DNA hybrids) or Topoisomerase 1 (an enzyme that relieves DNA supercoiling) can suppress the mcm2DENQ DNA-damage phenotype. Moreover, the observed DNA damage has several additional unusual properties, in that DNA damage foci appear only after S-phase, in G2/M, and are dependent upon progression into metaphase. In addition, we show that the resultant DNA damage is not due to spontaneous S-phase fork collapse. In total, these unusual mcm2DENQ phenotypes are markedly similar to those of a special previously-studied allele of the checkpoint sensor kinase ATR/MEC1, suggesting a possible regulatory interplay between Mcm2-7 and ATR during unchallenged growth. As RNA:DNA hybrids primarily result from transcription perturbations, we suggest that surveillance-mediated modulation of the Mcm2-7 activity plays an important role in preventing catastrophic conflicts between replication forks and transcription complexes. Possible relationships among these effects and the recently discovered role of Mcm2-7 in the DNA replication checkpoint induced by HU treatment are discussed.
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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.