The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
RPA2 Is a Direct Downstream Target for ATR to Regulate the S-phase Checkpoint
Open accessAbstract
Upon DNA damage, replication is inhibited by the S-phase checkpoint. ATR (ataxia telangiectasia mutated- and Rad3-related) is specifically involved in the inhibition of replicon initiation when cells are treated with DNA damage-inducing agents that stall replication forks, but the mechanism by which it acts to prevent replication is not yet fully understood. We observed that RPA2 is phosphorylated on chromatin in an ATR-dependent manner when replication forks are stalled. Mutation of the ATR-dependent phosphorylation sites in RPA2 leads to a defect in the down-regulation of DNA synthesis following treatment with UV radiation, although ATR activation is not affected. Threonine 21 and serine 33, two residues among several phosphorylation sites in the amino terminus of RPA2, are specifically required for the UV-induced, ATR-mediated inhibition of DNA replication. RPA2 mutant alleles containing phospho-mimetic mutations at ATR-dependent phosphorylation sites have an impaired ability to associate with replication centers, indicating that ATR phosphorylation of RPA2 directly affects the replication function of RPA. Our studies suggest that in response to UV-induced DNA damage, ATR rapidly phosphorylates RPA2, disrupting its association with replication centers in the S-phase and contributing to the inhibition of DNA replication.
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Cites
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S Phase and G2 Arrests Induced by Topoisomerase I Poisons Are Dependent on ATR Kinase Function
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Maréchal, A., & Zou, L. (2015) · Cell Research · doi:10.1038/cr.2014.147 · Cited by 465
RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells
Arora, R., Lee, Y., Wischnewski, H., Brun, C. M., Schwarz, T., & Azzalin, C. M. (2014) · Nature Communications · doi:10.1038/ncomms6220 · Cited by 469
Single-Stranded DNA Orchestrates an ATM-to-ATR Switch at DNA Breaks
Shiotani, B., & Zou, L. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.024 · Cited by 353
DNA mismatch repair and the DNA damage response
Li, Z., Pearlman, A. H., & Hsieh, P. (2016) · DNA Repair · doi:10.1016/j.dnarep.2015.11.019 · Cited by 307
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Metadata
- Authors
- Olson, E., Nievera, C. J., Klimovich, V., Fanning, E., & Wu, X.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 281
- Issue
- 51
- Pages
- 39517-39533
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2015946135
- Cited by
- 190
- References
- 13
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Olson, E., Nievera, C. J., Klimovich, V., Fanning, E., & Wu, X. (2006). RPA2 Is a Direct Downstream Target for ATR to Regulate the S-phase Checkpoint. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m605121200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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