The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways.
Open accessAbstract
SPK1/RAD53/MEC2/SAD1 of Saccharomyces cerevisiae encodes an essential protein kinase that is required for activation of replication-sensitive and DNA damage-sensitive checkpoint arrest. We have investigated the regulation of phosphorylation and kinase activity of Spk1p during the cell cycle and by conditions that activate checkpoint pathways. Phosphorylation of Spk1p is induced by treatment of cells with agents that damage DNA or interfere with DNA synthesis. Although only S- and G2-phase cdc mutants arrest with hyperphosphorylated Spk1p, damage-induced phosphorylation of Spk1p can occur in G1 and M as well. Hydroxyurea (HU) induces phosphorylation of kinase-defective forms of Spk1p, demonstrating that this regulated phosphorylation of Spk1p occurs in trans. HU-induced phosphorylation is associated with increased catalytic activity of Spk1p. Furthermore, overexpression of wild-type SPK1, but not checkpoint-defective alleles, delays progression through the G1/S boundary. Damage-dependent phosphorylation of Spk1p requires both MEC1 and MEC3, whereas MEC1 but not MEC3, is required for replication block-induced phosphorylation. These data support the model that Spk1p is an essential intermediate component in a signal transduction pathway coupling damage and checkpoint functions to cell cycle arrest. This regulation is mediated through a protein kinase cascade that potentially includes Mec1p and Tel1p as the upstream kinases.
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“Mec1 controls the checkpoint by direct phosphorylation of target proteins but also via phosphorylation of downstream effector kinases, most notably the kinases Rad53 and Chk1 (11, 43, 49).”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in Saccharomyces cerevisiae (2010) · cites this paper as [49]
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Cites
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Pâques, F., & Haber, J. E. (1999) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.63.2.349-404.1999 · Cited by 2,120
Liu, Q., Guntuku, S., Cui, X.-S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A., et al. (2000) · Genes & Development · doi:10.1101/gad.14.12.1448 · Cited by 1,625
Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase
Matsuoka, S. (1998) · Science · doi:10.1126/science.282.5395.1893 · Cited by 1,322
Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage
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Metadata
- Authors
- Sun, Z., Fay, D. S., Marini, F., Foiani, M., & Stern, D. F.
- Affiliations
- Yale University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1996-02-15
- Volume
- 10
- Issue
- 4
- Pages
- 395-406
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2150688223
- Cited by
- 300
- References
- 52
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- American Cancer Society
- National Heart, Lung, and Blood Institute (R01HL175156)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- Mec1, Tel1, DNA damage checkpoint, DNA replication checkpoint, protein phosphorylation, checkpoint signaling, cell cycle arrest, G1/S transition, hydroxyurea, kinase cascade, Saccharomyces cerevisiae
- MeSH terms
- Alkaline Phosphatase, Cell Cycle, Cell Division, DNA Damage, DNA Replication, DNA, Fungal, Fungal Proteins, Genes, Fungal, Hydroxyurea, Methyl Methanesulfonate, Phosphorylation, Precipitin Tests, Protein Kinases, Saccharomyces cerevisiae, Temperature, Immunoblotting, Signal Transduction, Gene Expression Regulation, Fungal, Mutagenesis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Checkpoint Kinase 2
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