Affinage

CDS1

Serine/threonine-protein kinase Chk2 · UniProt O96017

Length
543 aa
Mass
60.9 kDa
Annotated
2026-06-09
53 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The CDS1 symbol in this corpus resolves to two mechanistically distinct proteins. The dominant body of evidence describes a checkpoint serine/threonine kinase (the fission yeast Cds1 and its human ortholog HuCds1/CHK2) that enforces the S-phase replication checkpoint in response to DNA damage and replication arrest (PMID:9450932, PMID:10097108). This kinase is activated in a two-stage mechanism: the replication mediator Mrc1 recruits Cds1 to stalled forks through phospho-dependent interactions between Rad3-phosphorylated Mrc1 and the Cds1 FHA domain, enabling Rad3/ATM-dependent priming phosphorylation (Thr-11 in fission yeast, Thr-68 in human Cds1), after which primed molecules dimerize via the FHA domain and activate by trans-autophosphorylation of activation-loop residue Thr-328, with the C-terminal tail acting as an autoinhibitory element on unprimed monomers (PMID:11025670, PMID:11313465, PMID:15173168, PMID:16618806, PMID:19357077). Activated Cds1 phosphorylates Cdc25 on multiple serines to promote 14-3-3 binding and block Cdc2 activation, phosphorylates the Cdc2 inhibitor Wee1 and stabilizes Mik1, and phosphorylates p53 at DNA-damage-inducible sites, thereby coupling fork arrest to cell-cycle delay (PMID:9572736, PMID:9774107, PMID:10673501). At the fork, Cds1 controls genome stability by FHA-dependent phosphorylation of the Mus81 endonuclease, driving its dissociation from chromatin to prevent cleavage of stalled forks, and by regulating the repair proteins Rad60 and the phosphatase Flp1 (PMID:15805465, PMID:12897162, PMID:18385517). A separate, biochemically unrelated set of findings identifies CDS1 as an essential integral ER-membrane CDP-diacylglycerol synthase that converts phosphatidic acid to CDP-diacylglycerol for phosphatidylinositol and phosphoinositide synthesis (PMID:8557688). In mammalian cells this lipid enzyme is transcriptionally induced by sustained PLC/PKC/cFos signaling, is synthetically lethal with its paralog CDS2, and the CDS1/CDP-DAG axis modulates phosphoinositide-dependent signaling and tumor biology (PMID:30862571, PMID:40615675, PMID:41407218). Because the kinase findings and the lipid-synthase findings describe fundamentally distinct activities, they are reported separately and not as one protein.

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Established that Cds1 is a checkpoint kinase activated specifically during S phase, defining an S-phase-specific arm of the DNA damage/replication checkpoint distinct from the general checkpoint response.

    Evidence Genetic epistasis with checkpoint rad mutants, kinase assays, and Cds1-Rad26 co-IP in fission yeast

    PMID:9450932

    Open questions at the time
    • Did not define direct substrates
    • Did not resolve how the S-phase signal reaches Cds1
  2. 1998 High

    Identified the downstream effectors linking Cds1 to mitotic inhibition, showing it acts through Wee1, Mik1, and Cdc25 to restrain Cdc2.

    Evidence Genetic epistasis (cds1 chk1 double mutants), kinase assays, Wee1/Cdc25 phosphosite mapping and 14-3-3 binding assays in fission yeast

    PMID:9572736 PMID:9774107

    Open questions at the time
    • Did not establish the upstream Cds1 activation mechanism
    • Relative contribution of each effector to arrest unresolved
  3. 1999 High

    Demonstrated that the human ortholog HuCds1/CHK2 conserves the checkpoint function, responding to ionizing radiation in an ATM-dependent manner and to hydroxyurea ATM-independently, and phosphorylating Cdc25C.

    Evidence In vitro kinase assays on Cdc25C, 14-3-3 binding assays, ATM-deficient cell lines with IR and HU treatment

    PMID:10097108 PMID:9889122

    Open questions at the time
    • Priming phosphorylation site not yet identified
    • Mechanism of FHA-mediated activation not addressed
  4. 2000 High

    Defined the ATM priming site Thr-68 on human Cds1 and identified p53 as a substrate, linking the kinase to G1 arrest and the p53 damage response.

    Evidence In vitro ATM phosphorylation of T68, T68A mutagenesis with G1 arrest assays, and in vitro p53 phosphorylation comparing tetrameric vs monomeric substrate

    PMID:10673501 PMID:11025670

    Open questions at the time
    • Did not address the activation-loop autophosphorylation step
    • In vivo significance of p53 phosphorylation not quantified
  5. 2001 High

    Identified the fission yeast priming site Thr-11 and established Mrc1 as the mediator that channels the replication-arrest signal from Rad3 to Cds1.

    Evidence In vitro Rad3/ATM kinase assays on Cds1 T11, T11A mutagenesis with HU-sensitivity and checkpoint assays, and Mrc1-Cds1 co-IP with mrc1 deletion analysis

    PMID:11313465 PMID:11715017

    Open questions at the time
    • Did not define how Mrc1 physically engages Cds1
    • Activation-loop and dimerization steps still open
  6. 2003 High

    Linked Cds1 to fork stabilization and recombinational repair through the fork-protection factor Swi1 and the repair protein Rad60.

    Evidence Genetic epistasis (swi1 cds1), Rad22 foci, chromatin fractionation, and Cds1-Rad60 co-IP with kinase and localization assays in fission yeast

    PMID:12897162 PMID:14560029

    Open questions at the time
    • Did not establish direct biochemical hierarchy among fork factors
    • Functional consequence of Rad60 delocalization on repair outcome incompletely defined
  7. 2004 High

    Resolved the recruitment mechanism, showing phosphorylated Mrc1 engages the Cds1 FHA domain to enable Rad3-Rad26-dependent Thr-11 priming, bypassable by a Rad26-Cds1 fusion.

    Evidence Yeast two-hybrid, FHA domain mutagenesis, Rad26-Cds1 fusion rescue, and in vivo T11 phosphorylation in fission yeast

    PMID:15173168

    Open questions at the time
    • Did not define the dimerization/autoactivation step
    • Stoichiometry of the recruitment complex unresolved
  8. 2005 High

    Defined how Cds1 protects stalled forks, showing FHA-dependent phosphorylation of Mus81 drives its dissociation from chromatin to prevent endonucleolytic cleavage.

    Evidence FHA-binding-motif mutant co-IP, in vivo phosphorylation, chromatin fractionation, and mutator phenotype assays in fission yeast

    PMID:11073977 PMID:15805465

    Open questions at the time
    • Did not quantify fork restart kinetics after Mus81 removal
    • Whether other nucleases are similarly regulated unknown
  9. 2006 High

    Assembled the complete two-stage activation model: Mrc1-FHA recruitment plus Rad3 priming, then phospho-FHA-mediated dimerization and autophosphorylation.

    Evidence Biochemical reconstitution with FHA interaction mapping, phosphosite analysis, dimerization and in vitro kinase assays

    PMID:16618806

    Open questions at the time
    • Did not pinpoint the single residue sufficient for catalytic activation
    • Structural basis of FHA dimer not resolved
  10. 2009 High

    Identified the activation-loop residue Thr-328 as the sole modification required for catalysis and defined the C-terminal tail as an autoinhibitory element.

    Evidence In vitro kinase assays with phosphosite mutagenesis, trans-autophosphorylation assays, and C-terminal truncation analysis

    PMID:19357077 PMID:19596787

    Open questions at the time
    • Structural mechanism of tail-mediated autoinhibition not solved
    • Conservation of T328 regulation in human CHK2 not addressed here
  11. 2000 Medium

    Extended Cds1 checkpoint signaling to vertebrates, showing Xenopus Cds1 responds selectively to double-stranded DNA ends and constitutively associates with an ATR complex regulated by DNA-PK-primed phosphorylation.

    Evidence Cell-free egg extracts with immunodepletion, XCds1-ATR co-IP, domain mutagenesis, and sequential phosphorylation mapping

    PMID:10793133 PMID:11591827 PMID:15509799

    Open questions at the time
    • Negative result for checkpoint delay leaves XCds1's effector role unclear
    • SH3-binding-region engagement mapped indirectly
  12. 1996 High

    Established the unrelated CDS1 lipid-enzyme identity: an essential CDP-diacylglycerol synthase providing the bulk of cellular activity and controlling the balance of phosphatidylinositol synthesis.

    Evidence Null-mutant lethality, GAL1-driven overexpression, in vitro CDP-DAG synthase activity assays, and phospholipid measurement in S. cerevisiae

    PMID:8557688

    Open questions at the time
    • No structural or catalytic-mechanism detail
    • Relationship to the kinase-named Cds1 is none — distinct protein
  13. 2025 Medium

    Established the mammalian CDS1 lipid enzyme as a paralog-redundant, signaling-regulated node, synthetically lethal with CDS2 and modulating phosphoinositide-dependent pathways and tumor biology.

    Evidence PLC/PKC/cFos pharmacological dissection with qRT-PCR; CRISPR paired-gene screens with CDS1 re-expression rescue; in vivo lipid and PI3K/AKT readouts in cancer and asthma models

    PMID:30862571 PMID:40566856 PMID:40615675 PMID:41161459 PMID:41407218

    Open questions at the time
    • Direct enzymatic kinetics of human CDS1 not measured here
    • Mechanistic link from CDP-DAG to downstream phenotypes incompletely defined
    • Tissue-specific contributions of CDS1 vs CDS2 not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the two distinct CDS1 activities (checkpoint kinase versus CDP-diacylglycerol synthase) relate in this corpus, and whether the human kinase activation mechanism mirrors the dissected fission yeast pathway in full.
  • No discovery reconciles the kinase and lipid-synthase identities
  • Human CHK2 activation-loop and autoinhibition steps not directly tested in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0140657 ATP-dependent activity 3 GO:0016740 transferase activity 2 GO:0016874 ligase activity 1
Localization
GO:0005634 nucleus 2 GO:0005783 endoplasmic reticulum 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1430728 Metabolism 3 R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 3
Partners
CDC25CDS2CEBPGMRC1MUS81RAD26RAD60

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Fission yeast Cds1 kinase is phosphorylated and activated specifically during S phase in response to DNA damage or replication arrest (hydroxyurea), but not during G1 or G2. Activation requires all six checkpoint Rad proteins, and Cds1 interacts physically with Rad26. Cds1 is required to slow S phase in the presence of DNA-damaging agents and defines an S-phase-specific subpathway of the checkpoint response. Genetic epistasis (checkpoint rad mutants), kinase activity assays, co-immunoprecipitation (Cds1-Rad26 interaction), cell-cycle-stage-specific activation experiments Genes & development High 9450932
1998 In fission yeast, hydroxyurea-induced replication arrest stimulates Cds1 kinase, which phosphorylates Wee1 (an inhibitor of Cdc2) and is required for HU-induced increase in Mik1 (a second Cdc2 inhibitor). Cds1 and Chk1 jointly enforce the replication checkpoint; cds1 chk1 double mutants abolish HU-induced cell division arrest. Genetic epistasis (cds1 chk1 double mutants), kinase assays, western blotting for Mik1 levels Science (New York, N.Y.) High 9572736
1998 Fission yeast Cds1 and Chk1 both phosphorylate Cdc25 at serine residues 99, 192, and 359. Phosphorylation promotes Cdc25 binding to 14-3-3 proteins, preventing Cdc25 from activating Cdc2. Mutation of these residues reduces 14-3-3 binding in vitro and disrupts the replication checkpoint in vivo. In vitro kinase assays, mutagenesis of Cdc25 phosphorylation sites, 14-3-3 binding assays, in vivo checkpoint assays Nature High 9774107
1999 Human Cds1 (HuCds1/CHK2) is phosphorylated and activated in response to ionizing radiation in an ATM-dependent manner, and in response to hydroxyurea via an ATM-independent pathway. Like fission yeast Cds1, human Cds1 phosphorylates Cdc25C to promote 14-3-3 protein binding. In vitro kinase assay (Cdc25C phosphorylation), 14-3-3 binding assay, ATM-deficient cell lines, ionizing radiation and hydroxyurea treatment Proceedings of the National Academy of Sciences of the United States of America High 10097108
1999 Human Cds1 directly phosphorylates and inactivates Cdc25 in vitro. Human Cds1 kinase activity is activated in response to ionizing radiation in an ATM- and wortmannin-sensitive manner. In vitro kinase assay, Cdc25 activity assay, wortmannin inhibition, ATM-deficient cells Current biology : CB High 9889122
1999 Fission yeast Cds1 and Chk1 phosphorylate Cdc25 predominantly on serine-99 in vitro. Cds1 inhibits Cdc25-dependent activation of Cdc2 in vitro and contributes to mitotic delay in vivo. The Cdc25 S99A mutation partially impairs both S-M replication and G2-M damage checkpoints. In vitro kinase assay with phosphosite mapping, Cdc2 activation assay, in vivo checkpoint assay with S99A mutant Molecular biology of the cell High 10198041
2000 Human Cds1 (Chk2) phosphorylates p53 at multiple DNA damage-inducible sites in vitro, with preference for tetrameric over monomeric p53. Cds1 phosphorylates similar sites to Chk1 kinase. In vitro kinase assay with recombinant proteins, comparison of tetrameric vs. monomeric p53 substrates Genes & development High 10673501
2000 Threonine 68 of human Cds1 (Chk2) is the preferred ATM phosphorylation site in vitro and is the principal irradiation-induced phosphorylation site in vivo. A T68A non-phosphorylatable mutant fails to be fully activated and has reduced ability to induce G1 arrest in response to ionizing radiation. In vitro phosphorylation assay (ATM on Cds1 T68), site-directed mutagenesis (T68A), in vivo phosphorylation mapping, G1 arrest assay Nature cell biology High 11025670
2000 The FHA1 domain of fission yeast Cds1 interacts with the damage tolerance protein Mus81. Mus81 has an XPF-like endonuclease domain and is required for survival of replicational stress, UV radiation, and DNA polymerase impairment. Genetic epistasis suggests Mus81 works with recombination enzymes and that Mus81 inactivation triggers a checkpoint-dependent mitotic delay. Co-immunoprecipitation (Cds1 FHA1 domain – Mus81), genetic epistasis, loss-of-function phenotypic analysis Molecular and cellular biology High 11073977
1999 Checkpoint signal specificity: Cds1 becomes more highly concentrated in the nucleus specifically during S phase, correlating with S-phase specificity of IR-induced Cds1 activation. Cds1 actively suppresses Chk1 phosphorylation in HU-arrested cells, suggesting Cds1 prevents a repair process that would lead to Chk1 activation. Subcellular fractionation/localization of Cds1, epistasis analysis with cds1 mutants, HU arrest and IR treatment combinations Molecular and cellular biology Medium 10330167
2001 Fission yeast Mrc1 (mediator of replication checkpoint) associates with Cds1 and is required for Cds1 activation by Rad3. Mrc1 is cell-cycle-regulated, appearing coincident with S phase, and channels the replication arrest signal to Cds1. Co-immunoprecipitation (Mrc1-Cds1 interaction), kinase activation assays, mrc1 deletion phenotype analysis, mRNA/protein expression timing Nature cell biology High 11715017
2001 Fission yeast Rad3 (ATR homolog) and human ATM phosphorylate the N-terminal domain of Cds1 at threonine-11 (T11Q motif) in vitro. T11A substitution abolishes Cds1 activation by hydroxyurea, prevents S-M checkpoint enforcement, and renders cells profoundly HU-sensitive. In vitro kinase assay (Rad3/ATM phosphorylation of Cds1), site-directed mutagenesis (T11A), HU sensitivity assay, checkpoint enforcement assay Molecular and cellular biology High 11313465
2003 Fission yeast Swi1 (Tof1 homolog) is required for proficient activation of Cds1 at stalled replication forks. Swi1 and Cds1 together prevent fork collapse in rDNA repeats and at a hydroxyurea pause site. Swi1 is recruited to chromatin during S phase. Genetic epistasis (swi1 cds1 double mutants), Rad22 foci (marker of fork collapse), chromatin fractionation for Swi1 recruitment, Mus81 epistasis Molecular and cellular biology High 14560029
2003 Fission yeast Cds1 interacts with Rad60 (a recombinational repair protein). Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization. A Rad60 mutant resistant to Cds1 regulation renders cells specifically sensitive to replication fork arrest. Rad60 functions codependently with the SMC5/6 complex. Co-immunoprecipitation (Cds1-Rad60), kinase assay, subcellular localization (nuclear delocalization), HU sensitivity assay with Rad60 mutant, mass spectrometry Molecular and cellular biology High 12897162
2004 Mrc1 mediates initial Thr-11 phosphorylation of Cds1 by Rad3-Rad26 through specific interaction between phosphorylated Mrc1 and the FHA domain of Cds1 (demonstrated by yeast two-hybrid and FHA domain mutations). A Rad26-Cds1 fusion protein can bypass the requirement for Mrc1, indicating Mrc1 recruits Cds1 to Rad3-Rad26. Yeast two-hybrid (Mrc1-Cds1 FHA domain), FHA domain mutagenesis, Rad26-Cds1 fusion rescue, in vivo phosphorylation of T11 The Journal of biological chemistry High 15173168
2005 Cds1 regulates Mus81 via its FHA domain. A mutation in the Mus81 FHA-binding motif eliminates Cds1 binding and Cds1-dependent phosphorylation of Mus81. Upon acute HU treatment, extensive Cds1-dependent phosphorylation of Mus81 causes its dissociation from chromatin, preventing cleavage of stalled replication forks. Co-immunoprecipitation (Cds1 FHA – Mus81 motif mutant), in vivo phosphorylation assay, chromatin fractionation, mutator phenotype assay Genes & development High 15805465
2006 Cds1 activation occurs in two stages in fission yeast: (1) Mrc1 recruits Cds1 to stalled replication forks through interactions between the Cds1 FHA domain and Rad3-phosphorylated sites in Mrc1, followed by Rad3-dependent priming phosphorylation of Cds1; (2) primed Cds1 molecules dimerize via FHA domain phospho-specific interactions and are activated by autophosphorylation. Biochemical reconstitution, FHA domain interaction mapping, phosphorylation site analysis, dimerization assays, in vitro kinase assays Genes & development High 16618806
2008 Fission yeast Cds1 controls the release of the Cdc14-like phosphatase Flp1 from the nucleolus into the nucleus upon replication stress. Active Cds1 phosphorylates Flp1, and a Flp1 mutant lacking all Cds1 phosphorylation sites (flp1-9A) fails to relocate and shows checkpoint defects. Nuclear Flp1 in turn positively regulates full Cds1 activation (feedback loop). Subcellular localization by fluorescence microscopy, phosphorylation site mutagenesis (flp1-9A), kinase activity assays, Rad22 foci analysis Molecular biology of the cell High 18385517
2009 Cds1 activation loop residue Thr-328 is the only covalent modification required for kinase activation in vitro and in vivo, achieved through trans-autophosphorylation upon dimerization. The C-terminal 27-amino acid tail of Cds1 acts as an autoinhibitory element that prevents spontaneous activation of unprimed monomeric Cds1. In vitro kinase assay with phosphosite mutagenesis, trans-autophosphorylation assays, truncation analysis of C-terminal tail The Journal of biological chemistry High 19357077
2009 Fission yeast Cds1 phosphorylates APC/C activator Ste9 in vitro. At S-phase arrest, Cds1-dependent inhibition/phosphorylation of APC/C-Ste9 stabilizes the MBF activator Rep2 by preventing its ubiquitin-mediated proteolysis, thereby sustaining transcription of MBF-dependent genes needed for recovery. In vitro kinase assay (Cds1 phosphorylates Ste9), Rep2 ubiquitination assay, genetic analysis of Rep2 stability in cds1 mutants Molecular and cellular biology Medium 19596787
2000 Xenopus Cds1 (Xcds1) is phosphorylated and activated by the presence of DNA molecules with double-stranded ends in cell-free egg extracts. This activation is distinct from Xchk1, which responds to DNA replication blocks but not double-stranded ends. Immunodepletion of Xcds1 did not attenuate cell cycle delay induced by double-stranded DNA ends. Cell-free Xenopus egg extract system, immunodepletion, kinase activation assays, aphidicolin vs. dsDNA end comparison Molecular biology of the cell Medium 10793133
2004 In Xenopus, XCds1 constitutively associates with a Xenopus ATR complex under normal conditions via a putative SH3-binding region (not requiring functional FHA domain). In response to double-stranded DNA ends, DNA-PK phosphorylates XCds1 at serine-39 first, followed by ATM/ATR/DNA-PK phosphorylation of SQ sites, promoting dissociation from ATR complex and full activation of XCds1. Co-immunoprecipitation (XCds1-ATR complex), domain mutagenesis (FHA, SH3-binding region), sequential phosphorylation mapping, kinase activation assays Molecular and cellular biology Medium 15509799
2001 Xenopus Cds1 (XCds1) kinase activity is high in immature oocytes arrested at G2 and decreases at the meiotic G2/M transition. Overexpressed wild-type (but not kinase-deficient) XCds1 delays M-phase entry. XCds1 inactivation at G2/M depends on cyclin B-Cdc2 kinase activation, but XCds1 is not directly inactivated by Cdc2 in vitro. Kinase activity assays across oocyte maturation stages, overexpression of WT and kinase-dead XCds1, cyclin B overexpression, in vitro Cdc2 inactivation assay (negative result for direct inactivation) Journal of cell science Medium 11591827
2005 Cds1 is required in fission yeast meiosis to suppress DNA double-strand break (DSB) formation when premeiotic S phase is inhibited by hydroxyurea. Cds1 deletion restores DSB formation in the presence of HU in rad3 mutant background. Cds1 is required for suppression of mei4+ transcription factor and cdc25+ phosphatase transcription in HU-arrested meiotic cells. Genetic analysis (cds1 deletion in meiosis), DSB detection (gel analysis), transcriptional analysis of mei4+ and cdc25+, HU treatment The Journal of biological chemistry Medium 16286472
1996 The S. cerevisiae CDS1 gene encodes CDP-diacylglycerol synthase, is essential for cell growth (null mutants cannot germinate or grow vegetatively), and accounts for the majority of CDP-diacylglycerol synthase activity in the cell. Overexpression elevates phosphatidylinositol synthesis relative to phosphatidylserine. Null mutant construction, GAL1-driven overexpression, enzyme activity assay (CDP-diacylglycerol synthase), phospholipid synthesis measurement The Journal of biological chemistry High 8557688
2019 In mammalian H9c2 cardiomyoblasts, vasopressin-induced sustained phospholipase C activation selectively increases CDS1 mRNA through a protein kinase C- and cFos-dependent pathway (AP-1 signaling). CDS1 and CDS2 are integral ER membrane proteins in mammalian cells; CDS1 upregulation provides a mechanism for maintaining phosphatidylinositol levels during prolonged PLC signaling. Pharmacological inhibition (PKC inhibitor, AP-1 inhibitor T-5224), qRT-PCR for CDS1 mRNA, western blot for cFos, vasopressin stimulation assay Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 30862571
2025 CDS1 and CDS2 form a synthetic lethal pair in uveal melanoma: CDS2 is a genetic dependency specifically when CDS1 expression is low. CDS2 knockout disrupts phosphoinositide synthesis and increases cellular apoptosis; re-expression of CDS1 rescues the cell fitness defect, demonstrating functional redundancy between the two CDP-diacylglycerol synthase paralogs. CRISPR-Cas9 genome-wide and combinatorial paired-gene screens, in vivo validation, phosphoinositide synthesis measurement, CDS1 re-expression rescue Nature genetics High 40615675
2025 CDS1 catalyzes synthesis and secretion of CDP-diacylglycerol (CDP-DAG) in colorectal cancer cells. CDP-DAG binds transcription factor CEBPG and induces ferroptosis in myeloid-derived suppressor cells (MDSCs), relieving MDSC-mediated immunosuppression and enhancing cytotoxic T lymphocyte infiltration. CDP-DAG shows synergistic effects with anti-PDL1 therapy. In vitro and in vivo CDS1 loss-of-function models, MDSC ferroptosis assay, CEBPG binding assay, immune cell infiltration analysis, anti-PDL1 combination experiments Cellular signalling Medium 41161459
2025 CDS1 acts as a suppressor of nasopharyngeal carcinoma by decreasing intracellular lipid droplet formation. Restoring CDS1 expression suppresses NPC cell growth, migration, and invasion. CDS1 also promotes NF-κB pathway activation, increasing inflammatory cytokines and enhancing tumor immunogenicity in vivo. CDS1 re-expression in NPC cells, lipid droplet quantification, colony formation and invasion assays, in vivo tumor model, NF-κB pathway analysis Cell adhesion & migration Medium 40566856
2025 CDS1 downregulation in asthmatic epithelium results in decreased synthesis of phosphatidylinositol (PI) and PI(4,5)P2, suppressing PI3K/AKT signaling. CDS1 overexpression reverses the protective effects of bacterial cellulose on asthma in vivo, confirming CDS1 as a key node linking CDP-diacylglycerol/phosphoinositide metabolism to PI3K/AKT pathway activity. BALF metabolomics, single-cell RNA sequencing, CDS1 overexpression in vivo (mouse asthma model), PI and PIP2 measurement, PI3K/AKT pathway readouts International journal of biological macromolecules Medium 41407218

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes & development 726 10673501
1998 S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe. Genes & development 342 9450932
1998 Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1. Nature 314 9774107
1998 Replication checkpoint enforced by kinases Cds1 and Chk1. Science (New York, N.Y.) 286 9572736
2000 Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1. Nature cell biology 266 11025670
1999 A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Current biology : CB 240 9889122
2000 Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Molecular and cellular biology 238 11073977
1999 A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 238 10097108
2001 Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1. Nature cell biology 207 11715017
2000 Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. Journal of cell science 179 11058076
1999 Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1. Molecular biology of the cell 176 10198041
2003 Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1. Molecular and cellular biology 139 14560029
1996 The CDS1 gene encoding CDP-diacylglycerol synthase in Saccharomyces cerevisiae is essential for cell growth. The Journal of biological chemistry 121 8557688
2005 Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress. Genes & development 109 15805465
1999 Basis for the checkpoint signal specificity that regulates Chk1 and Cds1 protein kinases. Molecular and cellular biology 92 10330167
2002 Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor. BioEssays : news and reviews in molecular, cellular and developmental biology 83 12111733
1999 Role of human Cds1 (Chk2) kinase in DNA damage checkpoint and its regulation by p53. The Journal of biological chemistry 80 10531348
2003 Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60. Molecular and cellular biology 77 12897162
2006 Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast. Genes & development 75 16618806
2000 Response of Xenopus Cds1 in cell-free extracts to DNA templates with double-stranded ends. Molecular biology of the cell 70 10793133
1999 Genetic control of telomere integrity in Schizosaccharomyces pombe: rad3(+) and tel1(+) are parts of two regulatory networks independent of the downstream protein kinases chk1(+) and cds1(+). Genetics 59 10430579
2001 Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation of fission yeast checkpoint kinase Cds1. Molecular and cellular biology 50 11313465
2002 CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis. Genes and immunity 37 11857062
2004 Cds1 phosphorylation by Rad3-Rad26 kinase is mediated by forkhead-associated domain interaction with Mrc1. The Journal of biological chemistry 30 15173168
2018 Hydrolase CehA and Monooxygenase CfdC Are Responsible for Carbofuran Degradation in Sphingomonas sp. Strain CDS-1. Applied and environmental microbiology 29 29884759
2001 Critical role of Caenorhabditis elegans homologs of Cds1 (Chk2)-related kinases in meiotic recombination. Molecular and cellular biology 29 11158318
2008 Cds1 controls the release of Cdc14-like phosphatase Flp1 from the nucleolus to drive full activation of the checkpoint response to replication stress in fission yeast. Molecular biology of the cell 28 18385517
2005 Rad3-Cds1 mediates coupling of initiation of meiotic recombination with DNA replication. Mei4-dependent transcription as a potential target of meiotic checkpoint. The Journal of biological chemistry 27 16286472
2009 Autoinhibition and autoactivation of the DNA replication checkpoint kinase Cds1. The Journal of biological chemistry 21 19357077
1993 Iminium salt of copper benzochlorin (CDS1), a novel photosensitizer for photodynamic therapy: mechanism of cell killing. Photochemistry and photobiology 19 8378428
2001 Inactivation of the checkpoint kinase Cds1 is dependent on cyclin B-Cdc2 kinase activation at the meiotic G(2)/M-phase transition in Xenopus oocytes. Journal of cell science 18 11591827
2006 HIV-1 Vpr induces G2 cell cycle arrest in fission yeast associated with Rad24/14-3-3-dependent, Chk1/Cds1-independent Wee1 upregulation. Microbes and infection 16 16968670
2008 Involvement of fission yeast Clr6-HDAC in regulation of the checkpoint kinase Cds1. Nucleic acids research 14 18440981
2025 The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types. Nature genetics 11 40615675
2014 Meiotic nuclear movements in fission yeast are regulated by the transcription factor Mei4 downstream of a Cds1-dependent replication checkpoint pathway. Genes to cells : devoted to molecular & cellular mechanisms 10 25492408
2009 A Cds1-mediated checkpoint protects the MBF activator Rep2 from ubiquitination by anaphase-promoting complex/cyclosome-Ste9 at S-phase arrest in fission yeast. Molecular and cellular biology 10 19596787
2004 Xenopus Cds1 is regulated by DNA-dependent protein kinase and ATR during the cell cycle checkpoint response to double-stranded DNA ends. Molecular and cellular biology 10 15509799
2019 Sustained phospholipase C stimulation of H9c2 cardiomyoblasts by vasopressin induces an increase in CDP-diacylglycerol synthase 1 (CDS1) through protein kinase C and cFos. Biochimica et biophysica acta. Molecular and cell biology of lipids 9 30862571
2015 Casein kinase 1γ ensures monopolar growth polarity under incomplete DNA replication downstream of Cds1 and calcineurin in fission yeast. Molecular and cellular biology 8 25691662
2007 Characterization and physical mapping of the porcine CDS1 and CDS2 genes. Animal biotechnology 8 17364441
2005 Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis. Developmental dynamics : an official publication of the American Association of Anatomists 8 15937936
2008 Crosstalk between Nap1 protein and Cds1 checkpoint kinase to maintain chromatin integrity. Biochimica et biophysica acta 7 18474252
2014 Pcf1, a large subunit of CAF-1, required for maintenance of checkpoint kinase Cds1 activity. SpringerPlus 5 24478943
2009 The Schizosaccharomyces pombe checkpoint kinases Chk1 and Cds1 are important for cell survival in response to cisplatin. PloS one 4 19587778
2006 Methylation Inactivates Expression of CDP-diacylglycerol Synthase 1 (CDS1) in Hepatocellular Carcinoma. Cancer genomics & proteomics 4 31394702
2018 Nutrient Limitation Inactivates Mrc1-to-Cds1 Checkpoint Signalling in Schizosaccharomyces pombe. Cells 3 29473861
2004 Evolutionary conservation of a novel splice variant of the Cds1/CHK2 checkpoint kinase restricted to its regulatory domain. Cell cycle (Georgetown, Tex.) 3 15467464
2020 Mutation in histone deacetylase clr6 promotes the survival of S. pombe cds1 null mutant in response to hydroxyurea. Molecular genetics and genomics : MGG 1 32124033
2025 Loss of CDS1 impairs the tumorigenic characteristics of nasopharyngeal carcinoma by modulating lipid metabolism. Cell adhesion & migration 0 40566856
2025 CDS1 deficiency promotes colorectal cancer progression by suppressing CDP-DAG-induced ferroptosis in MDSCs. Cellular signalling 0 41161459
2025 Bacterial cellulose repairs asthmatic epithelial injury by reprogramming CDS1-mediated phosphatidylinositol metabolism to inhibit PI3K/AKT signaling. International journal of biological macromolecules 0 41407218
2007 [Dds20 operates in cds1-independent mechanism of tolerance to UV-induced DNA damage in Schizosaccharomyces pombe cells]. Genetika 0 17486762
2006 [Construction of double-labelled carbofuran-degrading bacterium Sphingomonas sp. CDS-1]. Wei sheng wu xue bao = Acta microbiologica Sinica 0 17037065

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