ArticleMolecular and cellular biology2006
Protein phosphatase 2A antagonizes ATM and ATR in a Cdk2- and Cdc7-independent DNA damage checkpoint.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
- Regulation of Virus Replication by BK Polyomavirus Small T Antigen.Journal of virology · 2023Article
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- Transcriptome Analysis of Caco-2 Cells upon the Exposure of Mycotoxin Deoxynivalenol and Its Acetylated Derivatives.Toxins · 2021Article
- On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway.Genes · 2019Review
- HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130.Nature communications · 2018Article
- Investigating the role of Rts1 in DNA replication initiation.Wellcome open research · 2018Article
- Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage.The Journal of biological chemistry · 2016Article
- Critical reanalysis of the methods that discriminate the activity of CDK2 from CDK1.Cell cycle (Georgetown, Tex.) · 2016Review
- The Adenovirus E4orf4 Protein Provides a Novel Mechanism for Inhibition of the DNA Damage Response.PLoS pathogens · 2016Article
- Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma.Molecular cancer therapeutics · 2015Article
- Protein phosphatase 2A and Cdc7 kinase regulate the DNA unwinding element-binding protein in replication initiation.The Journal of biological chemistry · 2014Article
- Article
- Adenovirus E4orf4 protein-induced death of p53-/- H1299 human cancer cells follows a G1 arrest of both tetraploid and diploid cells due to a failure to initiate DNA synthesis.Journal of virology · 2013Article
- Control of DNA replication by the nucleus/cytoplasm ratio in Xenopus.The Journal of biological chemistry · 2013Article
- Role for Rif1 in the checkpoint response to damaged DNA in Xenopus egg extracts.Cell cycle (Georgetown, Tex.) · 2012Article
- Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) protein to regulate intra-S-phase checkpoint.The Journal of biological chemistry · 2012Article
- What goes on must come off: phosphatases gate-crash the DNA damage response.Trends in biochemical sciences · 2011Review
- Phosphatases in the cellular response to DNA damage.Cell communication and signaling : CCS · 2010Article
- Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition.Oncogene · 2010Article
- The DNA unwinding element binding protein DUE-B interacts with Cdc45 in preinitiation complex formation.Molecular and cellular biology · 2010Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
We previously used a soluble cell-free system derived from Xenopus eggs to investigate the role of protein phosphatase 2A (PP2A) in chromosomal DNA replication. We found that immunodepletion of PP2A or inhibition of PP2A by okadaic acid (OA) inhibits initiation of DNA replication by preventing loading of the initiation factor Cdc45 onto prereplication complexes. Evidence was provided that PP2A counteracts an inhibitory protein kinase that phosphorylates and inactivates a crucial Cdc45 loading factor. Here, we report that the inhibitory effect of OA is abolished by caffeine, an inhibitor of the checkpoint kinases ataxia-telangiectasia mutated protein (ATM) and ataxia-telangiectasia related protein (ATR) but not by depletion of ATM or ATR from the extract. Furthermore, we demonstrate that double-strand DNA breaks (DSBs) cause inhibition of Cdc45 loading and initiation of DNA replication and that caffeine, as well as immunodepletion of either ATM or ATR, abolishes this inhibition. Importantly, the DSB-induced inhibition of Cdc45 loading is prevented by addition of the catalytic subunit of PP2A to the extract. These data suggest that DSBs and OA prevent Cdc45 loading through different pathways, both of which involve PP2A, but only the DSB-induced checkpoint implicates ATM and ATR. The inhibitory effect of DSBs on Cdc45 loading does not result from downregulation of cyclin-dependent kinase 2 (Cdk2) or Cdc7 activity and is independent of Chk2. However, it is partially dependent on Chk1, which becomes phosphorylated in response to DSBs. These data suggest that PP2A counteracts ATM and ATR in a DNA damage checkpoint in Xenopus egg extracts.
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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.