PANTHER family review PTHR11139: IBA propagation assessment for rad3
Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Automatic Gene Ontology annotation based on Rhea mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Requirement of sequences outside the conserved kinase domain of fission yeast Rad3p for checkpoint control.
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The isolated Rad3 kinase domain is necessary but not sufficient; sequences outside the kinase domain are required for catalytic activity, and PIKK-family members (including Rad3) have not been shown to phosphorylate lipids.
"Despite this similarity, none of the PI3-kinase-related (PI3KR) proteins have been shown to phosphorylate lipids."
Meiotic DNA replication checkpoint control in fission yeast.
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The meiotic DNA replication checkpoint requires the mitotic checkpoint Rad genes (including rad3) and Cds1.
"The mitotic checkpoint Rad genes and the Cds1 protein kinase are required for the DNA replication checkpoint during meiosis"
A Rad3-Rad26 complex responds to DNA damage independently of other checkpoint proteins.
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Rad3 forms a stable complex with Rad26 (ATR-ATRIP); Rad26 is phosphorylated in a Rad3-dependent manner after DNA damage independently of other checkpoint proteins.
"Here we report a stable association between Rad3 and Rad26 in soluble protein extracts. Rad26 shows Rad3-dependent phosphorylation after DNA damage."
Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation of fission yeast checkpoint kinase Cds1.
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Rad3 phosphorylates Cds1 at Thr-11 (T11Q12), required for Cds1 activation and the S-M checkpoint.
"Rad3-dependent phosphorylation of Cds1 at threonine-11 is required for Cds1 activation and function."
Serine-345 is required for Rad3-dependent phosphorylation and function of checkpoint kinase Chk1 in fission yeast.
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Rad3 directly phosphorylates Chk1 at Ser-345, required for the G2/M DNA damage checkpoint.
"Rad3 and ATM phosphorylate serine-345 of fission yeast Chk1. Mutation of serine-345 (chk1-S345A) abrogates Rad3-dependent phosphorylation of Chk1 in vivo."
A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway.
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The intra-S-phase checkpoint that slows DNA synthesis requires the checkpoint-Rad proteins and Cds1 and is triggered when forks encounter damage.
"The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1, and on Rad4/Cut5"
Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres.
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Rad3/Rad26 and Tel1/Rad32 are two redundant pathways required to maintain telomeres and prevent chromosome circularization; Rad3 associates with telomeres.
"Rad3/Rad26 and Tel1/Rad32 represent two pathways required to maintain telomeres and prevent chromosome circularization"
Replication checkpoint protein Mrc1 is regulated by Rad3 and Tel1 in fission yeast.
Regulation of checkpoint kinases through dynamic interaction with Crb2.
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Rad3 interacts directly with the mediator Crb2 and regulates Chk1 activation through dynamic Rad3-Crb2-Chk1 interactions.
"we show direct interaction between Rad3 and Crb2, which is inhibitory to Rad3 activity."
Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1.
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Rad3 phosphorylates the 9-1-1 clamp subunit Rad9 at T412/S423 to enable Chk1 activation.
"C-terminal T412/S423 phosphorylation of Rad9 by Rad3(ATR) occurs in S phase without replication stress. Rad3(ATR) and Tel1(ATM) phosphorylate these same residues"
Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast.
The rad3+ gene of Schizosaccharomyces pombe is involved in multiple checkpoint functions and in DNA repair.
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rad3 mutants fail G2 arrest after irradiation and fail to couple mitosis to completion of DNA synthesis; rad3 also contributes to DNA repair.
"the mutant cells are unable to arrest in the G2 phase of the cell cycle after DNA damage by gamma-irradiation and are also incapable of maintaining the dependence of mitosis upon the completion of DNA synthesis"
Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast.
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Cds1 is recruited by Mrc1 to stalled forks and primed by Rad3-dependent phosphorylation, then activated by FHA-mediated dimerization and autophosphorylation.
"Cds1 is then primed for activation by Rad3-dependent phosphorylation."
ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
Cdc18 enforces long-term maintenance of the S phase checkpoint by anchoring the Rad3-Rad26 complex to chromatin.
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Cdc18 anchors the Rad3-Rad26 complex to chromatin during stalled replication for long-term S-phase checkpoint maintenance.
"Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3 and Rad26."
Minichromosome maintenance proteins interact with checkpoint and recombination proteins to promote s-phase genome stability.
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Rad3 is required for Cds1 activation and protects stalled replication forks during hydroxyurea arrest; the paper does not present a Rad3 localization assay.
"This is also the case in Δ rad3 mutants, because the Rad3 kinase is required for Cds1 phosphorylation and activation."
Focused OpenScientist review of the rad3 GO:0005730 nucleolus annotation
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Focused full-text and cross-database review found no Rad3 localization assay in PMID:18180284 and recommended treating MARK_AS_OVER_ANNOTATED as a conservative floor pending inspection of separately hosted supplements.
"The seed action **MARK_AS_OVER_ANNOTATED is supported and, if anything, conservative.**"
Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint.
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Mus81/Rhp51/Rqh1 act in an epistatic pathway required for the S-phase DNA damage checkpoint with Rad3/Cds1.
"Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint."
A kinase-independent role for the Rad3(ATR)-Rad26(ATRIP) complex in recruitment of Tel1(ATM) to telomeres in fission yeast.
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The Rad3-Rad26 complex recruits Tel1 to telomeres independently of Rad3 kinase activity; Rad26 is required for Rad3 telomere association.
"the Rad3(ATR)-Rad26(ATRIP) complex contributes to the recruitment of Tel1(ATM) independently of Rad3(ATR) kinase activity"
The Mek1 phosphorylation cascade plays a role in meiotic recombination of Schizosaccharomyces pombe.
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Rad3 (and/or Tel1) phosphorylates the meiotic kinase Mek1 at S12/S14/T15 in response to meiotic DSBs.
"Mek1 is phosphorylated at serine-12 (S12), S14 and threonine-15 (T15) by Rad3 (ATR) and/or Tel1 (ATM) kinases that are activated by meiotic programmed double-strand breaks (DSBs)"
Hsk1 kinase and Cdc45 regulate replication stress-induced checkpoint responses in fission yeast.
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Hsk1 and Cdc45 regulate replication-stress checkpoint responses acting with the Rad3-Mrc1 pathway to activate Cds1.
"Hsk1 kinase and Cdc45 regulate replication stress-induced checkpoint responses in fission yeast."
Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1).
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Mcm10 interacts with Rad4/Cut5(TopBP1) at replication origins, the chromatin context where Rad3 surveys replication.
"Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1)."
Tel1(ATM) and Rad3(ATR) phosphorylate the telomere protein Ccq1 to recruit telomerase and elongate telomeres in fission yeast.
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Rad3 (with Tel1) phosphorylates Ccq1 at Thr-93 to recruit telomerase and elongate telomeres.
"the telomere protein Ccq1 is phosphorylated at Thr 93 (threonine residue at amino acid 93) by Tel1(ATM) and Rad3(ATR) both in vitro and in vivo"
The telomere bouquet facilitates meiotic prophase progression and exit in fission yeast.
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Persistent meiotic recombination damage activates the Rad3-Chk1 checkpoint, extending the meiotic prophase bouquet stage.
"Persistent DNA damages, induced during meiotic recombination, activate the Rad3 and Chk1 DNA damage checkpoint kinases and extend the bouquet stage beyond the chromosome oscillation period."
The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes.
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Atr (the ortholog of S. pombe Rad3) associates with unpaired/asynapsed axes of meiotic chromosomes, suggesting a direct role in recognizing meiotic DNA strand interruptions.
"Atr is found at sites along unpaired or asynapsed chromosomal axes"
The Schizosaccharomyces pombe rad3 checkpoint gene.
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Rad3 is the homolog of S. cerevisiae Mec1/Esr1 and Drosophila mei-41 and is closely related to human ATR; overexpressed Rad3 has associated protein kinase activity.
"immunoprecipitation of overexpressed Rad3 demonstrates an associated protein kinase activity"