ArticleProceedings of the National Academy of Sciences of the United States of America2012
Checkpoint kinase 2 (Chk2) inhibits the activity of the Cdc45/MCM2-7/GINS (CMG) replicative helicase complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Leading and lagging strand abasic sites differentially affect vertebrate replisome progression but involve analogous bypass mechanisms.Nucleic acids research · 2025Article
- Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.Molecular diagnosis & therapy · 2024Review
- Distinct functions of EHMT1 and EHMT2 in cancer chemotherapy and immunotherapy.bioRxiv : the preprint server for biology · 2023Article
- Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Rad53 limits CMG helicase uncoupling from DNA synthesis at replication forks.Nature structural & molecular biology · 2020Article
- Helicase Subunit Cdc45 Targets the Checkpoint Kinase Rad53 to Both Replication Initiation and Elongation Complexes after Fork Stalling.Molecular cell · 2019Article
- Potent DNA strand annealing activity associated with mouse Mcm2∼7 heterohexameric complex.Nucleic acids research · 2017Article
- Non-essential MCM-related proteins mediate a response to DNA damage in the archaeon Methanococcus maripaludis.Microbiology (Reading, England) · 2017Article
- Reconstitution of a eukaryotic replisome reveals the mechanism of asymmetric distribution of DNA polymerases.Nucleus (Austin, Tex.) · 2016Review
- Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells.International journal of oncology · 2016Article
- Replication stress: getting back on track.Nature structural & molecular biology · 2016Review
- Bacterial and Eukaryotic Replisome Machines.JSM biochemistry and molecular biology · 2016Article
- Sld3-MCM Interaction Facilitated by Dbf4-Dependent Kinase Defines an Essential Step in Eukaryotic DNA Replication Initiation.Frontiers in microbiology · 2016Article
- Phosphorylation of Minichromosome Maintenance 3 (MCM3) by Checkpoint Kinase 1 (Chk1) Negatively Regulates DNA Replication and Checkpoint Activation.The Journal of biological chemistry · 2015Article
- Domain within the helicase subunit Mcm4 integrates multiple kinase signals to control DNA replication initiation and fork progression.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Parvovirus-induced depletion of cyclin B1 prevents mitotic entry of infected cells.PLoS pathogens · 2014Article
- DNA replication and homologous recombination factors: acting together to maintain genome stability.Chromosoma · 2013Review
- Article
- Chemotherapy induced DNA damage response: convergence of drugs and pathways.Cancer biology & therapy · 2013Review
- The level of origin firing inversely affects the rate of replication fork progression.The Journal of cell biology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The replication of eukaryote chromosomes slows down when DNA is damaged and the proteins that work at the fork (the replisome) are known targets for the signaling pathways that mediate such responses critical for accurate genomic inheritance. However, the molecular mechanisms and details of how this response is mediated are poorly understood. In this report we show that the activity of replisome helicase, the Cdc45/MCM2-7/GINS (CMG) complex, can be inhibited by protein phosphorylation. Recombinant Drosophila melanogaster CMG can be stimulated by treatment with phosphatase whereas Chk2 but not Chk1 interferes with the helicase activity in vitro. The targets for Chk2 phosphorylation have been identified and reside in MCM subunits 3 and 4 and in the GINS protein Psf2. Interference requires a combination of modifications and we suggest that the formation of negative charges might create a surface on the helicase to allosterically affect its function. The treatment of developing fly embryos with ionizing radiation leads to hyperphosphorylation of Psf2 subunit in the active helicase complex. Taken together these data suggest that the direct modification of the CMG helicase by Chk2 is an important nexus for response to DNA damage.
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.