id: Q02099
gene_symbol: rad3
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:284812
  label: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
description: >-
  Rad3 is the fission-yeast ortholog of human ATR (and budding yeast Mec1), a large
  (2386 aa) PIKK-family (phosphatidylinositol-3-kinase-related) serine/threonine protein
  kinase (EC 2.7.11.1) that is the apical sensor kinase of the DNA-structure checkpoints,
  responding to both DNA damage and stalled/incomplete DNA replication. Despite its
  sequence similarity to lipid kinases, Rad3 is a protein kinase that phosphorylates
  serine or threonine residues within S/T-Q (SQ/TQ) motifs. It functions as a stable
  heterodimeric complex with its regulatory subunit Rad26 (ATRIP), which is recruited to
  RPA-coated single-stranded DNA at stalled forks and resected breaks. Together with the
  checkpoint clamp (Rad1-Rad9-Hus1, the 9-1-1 clamp) and the Rad17 clamp loader, the
  Rad3-Rad26 complex transduces the checkpoint signal by phosphorylating and activating
  the effector kinases Chk1 (DNA damage, G2/M arrest via Cdc25 inhibition) and Cds1
  (replication checkpoint, S-M coupling), as well as mediators such as Crb2, Mrc1 and
  Rad9, and the histone variant H2A (generating gamma-H2A). Rad3 also acts in meiotic
  checkpoints, in telomere maintenance (phosphorylating Ccq1 to recruit telomerase, and
  redundantly with Tel1/MRN preventing chromosome circularization), and contributes to
  telomere protection partly through kinase-independent functions of the Rad3-Rad26
  complex. It is a nuclear, chromatin-associated kinase that localizes to sites of DNA
  damage, stalled replication forks and telomeres.
existing_annotations:
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Core molecular function. Rad3/ATR is a protein serine/threonine kinase that
      phosphorylates SQ/TQ motifs in checkpoint substrates. Strongly supported by
      phylogenetic inference and abundant experimental data.
    action: ACCEPT
    reason: >-
      Rad3 is the apical checkpoint Ser/Thr kinase; multiple IDA/IMP annotations and direct
      substrate phosphorylation studies corroborate this phylogenetic call.
    supported_by:
    - reference_id: PMID:11553781
      supporting_text: >-
        Rad3, a protein kinase related to human ATM and ATR. These kinases phosphorylate
        serine or threonine followed by glutamine (SQ/TQ).
      reference_section_type: ABSTRACT
- term:
    id: GO:0000077
    label: DNA damage checkpoint signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Core biological process. Rad3 is the apical sensor kinase required for DNA damage
      checkpoint signaling, transducing damage signals to Chk1 to delay mitosis.
    action: ACCEPT
    reason: >-
      Phylogenetic inference corroborated by classic genetics (rad3 mutants fail G2 arrest
      after irradiation) and direct Chk1 phosphorylation.
    supported_by:
    - reference_id: PMID:1594599
      supporting_text: >-
        the mutant cells are unable to arrest in the G2 phase of the cell cycle after DNA
        damage by gamma-irradiation
      reference_section_type: ABSTRACT
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Rad3 acts on chromatin/chromosomes, including at sites of DNA damage, stalled
      replication forks and telomeres. The generic chromosome term is supported.
    action: ACCEPT
    reason: >-
      Consistent with chromatin and telomere ChIP localization; a more specific chromatin
      term is also annotated.
    supported_by:
    - reference_id: PMID:17531813
      supporting_text: >-
        Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3
        and Rad26.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      Correct but general parent term. The specific protein serine/threonine kinase
      activity term is preferred.
    action: MODIFY
    reason: >-
      Rad3 is specifically a protein Ser/Thr kinase; the more specific term is supported by
      experimental data, so this general term should be refined.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    supported_by:
    - reference_id: PMID:8978690
      supporting_text: >-
        immunoprecipitation of overexpressed Rad3 demonstrates an associated protein kinase
        activity
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Core molecular function, electronically inferred from EC 2.7.11.1 / InterPro. Fully
      consistent with experimental evidence.
    action: ACCEPT
    reason: Redundant with experimentally supported protein Ser/Thr kinase annotations.
    supported_by:
    - reference_id: PMID:11313465
      supporting_text: >-
        Rad3 and ATM phosphorylate the N-terminal domain of Cds1 at the motif T(11)Q(12)
      reference_section_type: ABSTRACT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rad3 is a nuclear protein (UniProt subcellular location), consistent with its role
      acting on chromatin and chromosomes.
    action: ACCEPT
    reason: Supported by UniProt subcellular location and chromatin/telomere localization data.
    supported_by:
    - reference_id: PMID:17531813
      supporting_text: >-
        Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3
        and Rad26.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006338
    label: chromatin remodeling
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: >-
      This term was inferred electronically (GO_REF:0000108) from Rad3's histone H2A kinase
      activity (GO:0140995) via a GO inter-ontology logical link. Rad3 genuinely
      phosphorylates histone H2A (gamma-H2A), so the inference is internally consistent
      with GO's logical definitions; however, "chromatin remodeling" most naturally denotes
      ATP-dependent nucleosome repositioning, and gamma-H2A is better understood as a
      DNA-damage signaling mark than as remodeling. The annotation is thus over-broad
      rather than strictly wrong.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Automated inter-ontology inference from Rad3's bona fide histone H2A kinase activity.
      gamma-H2A is a signaling mark; labeling Rad3 a chromatin "remodeler" over-reaches the
      inference, so the term is flagged as over-annotated rather than removed (the
      underlying histone-kinase function is real).
    supported_by:
    - reference_id: PMID:15226425
      supporting_text: >-
        formation of gamma-H2A redundantly requires the ATR/ATM-related kinases Rad3 and
        Tel1
      reference_section_type: ABSTRACT
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Overly general, derived from the PI3/PI4-kinase InterPro signature. As written it also
      risks implying lipid kinase activity, which is not supported - Rad3 is a protein
      Ser/Thr kinase. Should be refined to the specific protein kinase term.
    action: MODIFY
    reason: >-
      The PIKK signature reflects sequence similarity to lipid kinases, but Rad3 has not been
      shown to phosphorylate lipids; the informative activity is protein Ser/Thr kinase.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    supported_by:
    - reference_id: PMID:10512862
      supporting_text: >-
        Despite this similarity, none of the PI3-kinase-related (PI3KR) proteins have been
        shown to phosphorylate lipids.
      reference_section_type: INTRODUCTION
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Generic parent term. Rad3 is a checkpoint signal-transducing kinase, so this is not
      wrong, but the specific checkpoint signaling terms are far more informative.
    action: KEEP_AS_NON_CORE
    reason: >-
      Broadly correct but uninformative; the specific DNA damage/replication checkpoint
      signaling terms capture the function.
    supported_by:
    - reference_id: PMID:10559981
      supporting_text: >-
        Rad26 shows Rad3-dependent phosphorylation after DNA damage.
      reference_section_type: ABSTRACT
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      RHEA-derived MF consistent with Rad3 being a protein Ser/Thr kinase. The combined
      Ser/Thr term is preferred as primary, but this is accurate.
    action: ACCEPT
    reason: Accurate sub-aspect of the kinase activity; redundant with GO:0004674.
    supported_by:
    - reference_id: PMID:11553781
      supporting_text: >-
        Rad3 and ATM phosphorylate serine-345 of fission yeast Chk1.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14739927
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" is uninformative. This annotation records the Rad3-Crb2
      interaction; the functionally meaningful relationships (Rad3-Rad26 complex, Rad3
      phosphorylating Crb2/Chk1) are captured by other terms.
    action: REMOVE
    reason: >-
      Per curation guidelines, avoid uninformative protein binding; the relevant interaction
      is better represented by the ATR-ATRIP complex and substrate phosphorylation terms.
    supported_by:
    - reference_id: PMID:14739927
      supporting_text: >-
        we show direct interaction between Rad3 and Crb2, which is inhibitory to Rad3
        activity.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:10559981
  qualifier: located_in
  review:
    summary: >-
      Nuclear localization, consistent with Rad3 function. Supported, though the specific
      chromatin/chromosome and ATR-ATRIP complex terms are more informative.
    action: ACCEPT
    reason: Correct compartment, corroborated by multiple lines of evidence.
    supported_by:
    - reference_id: PMID:10559981
      supporting_text: >-
        a stable association between Rad3 and Rad26 in soluble protein extracts
      reference_section_type: ABSTRACT
- term:
    id: GO:0070310
    label: ATR-ATRIP complex
  evidence_type: IPI
  original_reference_id: PMID:10559981
  qualifier: part_of
  review:
    summary: >-
      Core cellular component. Rad3 (ATR) forms a stable complex with Rad26 (ATRIP), the
      canonical ATR-ATRIP DNA damage-sensing kinase complex.
    action: ACCEPT
    reason: Directly demonstrated stable Rad3-Rad26 complex; ComplexPortal CPX-26412.
    supported_by:
    - reference_id: PMID:10559981
      supporting_text: >-
        a stable association between Rad3 and Rad26 in soluble protein extracts
      reference_section_type: ABSTRACT
- term:
    id: GO:2000779
    label: regulation of double-strand break repair
  evidence_type: NAS
  original_reference_id: PMID:10559981
  qualifier: involved_in
  review:
    summary: >-
      Broadly consistent with Rad3's role as a checkpoint kinase that governs the DNA-damage
      response to double-strand breaks, but this is an NAS, general annotation rather than a
      core function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Plausible regulatory role via checkpoint signaling, but not the primary, directly
      assayed function.
    supported_by:
    - reference_id: PMID:10559981
      supporting_text: >-
        Rad3-related checkpoint kinases may have a direct role in DNA-damage recognition.
      reference_section_type: ABSTRACT
- term:
    id: GO:0140995
    label: histone H2A kinase activity
  evidence_type: EXP
  original_reference_id: PMID:15226425
  qualifier: enables
  review:
    summary: >-
      Experimentally supported specific molecular function. Rad3, redundantly with Tel1,
      phosphorylates the C-terminal SQE motif of histone H2A to generate gamma-H2A at sites
      of DNA damage.
    action: ACCEPT
    reason: Direct experimental evidence that gamma-H2A formation requires Rad3 and Tel1.
    supported_by:
    - reference_id: PMID:15226425
      supporting_text: >-
        formation of gamma-H2A redundantly requires the ATR/ATM-related kinases Rad3 and
        Tel1
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:15155581
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 phosphorylates the 9-1-1 clamp subunit Rad9 on C-terminal SQ/TQ sites
      (T412/S423), required for Chk1 checkpoint activation.
    action: ACCEPT
    reason: Direct evidence of Rad3-dependent Rad9 SQ/TQ phosphorylation.
    supported_by:
    - reference_id: PMID:15155581
      supporting_text: >-
        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
      reference_section_type: ABSTRACT
- term:
    id: GO:0033315
    label: meiotic G2/MI DNA replication checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:10521402
  qualifier: involved_in
  review:
    summary: >-
      Supported. The meiotic DNA replication checkpoint that blocks meiosis I when
      replication is incomplete requires the mitotic checkpoint Rad genes (including rad3)
      and Cds1.
    action: ACCEPT
    reason: Genetic evidence that the meiotic replication checkpoint requires the Rad genes.
    supported_by:
    - reference_id: PMID:10521402
      supporting_text: >-
        The mitotic checkpoint Rad genes and the Cds1 protein kinase are required for the
        DNA replication checkpoint during meiosis
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10559981
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" recording the Rad3-Rad26 interaction. The Rad3-Rad26
      relationship is informatively captured by the ATR-ATRIP complex term.
    action: REMOVE
    reason: >-
      Uninformative per curation guidelines; the Rad26 (ATRIP) interaction is represented by
      the ATR-ATRIP complex annotation.
    supported_by:
    - reference_id: PMID:10559981
      supporting_text: >-
        a stable association between Rad3 and Rad26 in soluble protein extracts
      reference_section_type: ABSTRACT
- term:
    id: GO:0070310
    label: ATR-ATRIP complex
  evidence_type: IDA
  original_reference_id: PMID:10559981
  qualifier: part_of
  review:
    summary: >-
      Core cellular component (IDA). Directly demonstrated Rad3-Rad26 (ATR-ATRIP) complex.
    action: ACCEPT
    reason: Direct co-purification of Rad3 with Rad26.
    supported_by:
    - reference_id: PMID:10559981
      supporting_text: >-
        a stable association between Rad3 and Rad26 in soluble protein extracts
      reference_section_type: ABSTRACT
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:8978690
  qualifier: enables
  review:
    summary: >-
      Correct but general; immunoprecipitated Rad3 shows associated protein kinase activity.
      The specific protein Ser/Thr kinase term is preferred.
    action: MODIFY
    reason: >-
      The activity is a protein Ser/Thr kinase; the more specific term is well supported.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    supported_by:
    - reference_id: PMID:8978690
      supporting_text: >-
        immunoprecipitation of overexpressed Rad3 demonstrates an associated protein kinase
        activity
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:16618806
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 is the upstream kinase that, with the mediator Mrc1, primes the
      replication checkpoint kinase Cds1 by Rad3-dependent phosphorylation.
    action: ACCEPT
    reason: Direct evidence of Rad3-dependent phosphorylation priming Cds1 activation.
    supported_by:
    - reference_id: PMID:16618806
      supporting_text: >-
        Cds1 is then primed for activation by Rad3-dependent phosphorylation.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:14585996
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 (with Tel1) phosphorylates the replication-checkpoint mediator Mrc1 at
      S/TQ motifs to control Cds1 activation.
    action: ACCEPT
    reason: Direct evidence of Rad3-dependent Mrc1 phosphorylation.
    supported_by:
    - reference_id: PMID:14585996
      supporting_text: >-
        Rad3 and Tel1 regulate Mrc1 through differential phosphorylation to control Cds1.
      reference_section_type: ABSTRACT
- term:
    id: GO:0051598
    label: meiotic recombination checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:29123917
  qualifier: involved_in
  review:
    summary: >-
      Supported. Persistent DNA damage from meiotic recombination activates the Rad3-Chk1
      checkpoint, extending meiotic prophase (the bouquet stage).
    action: ACCEPT
    reason: >-
      Live-imaging genetics show Rad3 (with Chk1) restrains meiotic prophase exit in
      response to unrepaired recombination intermediates.
    supported_by:
    - reference_id: PMID:29123917
      supporting_text: >-
        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.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:17531813
  qualifier: is_active_in
  review:
    summary: >-
      Supported cellular component. The Rad3-Rad26 complex is anchored to chromatin via
      Cdc18 during stalled replication to maintain the S-phase checkpoint.
    action: ACCEPT
    reason: Direct evidence of chromatin-bound Rad3-Rad26 complex.
    supported_by:
    - reference_id: PMID:17531813
      supporting_text: >-
        Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3
        and Rad26.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000723
    label: telomere maintenance
  evidence_type: IGI
  original_reference_id: PMID:20140190
  qualifier: involved_in
  review:
    summary: >-
      Supported. The Rad3-Rad26 complex contributes to telomere maintenance, including a
      kinase-independent role in recruiting Tel1 to telomeres. Important for genome
      stability but not the core checkpoint-kinase function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Genetic interaction evidence supports a telomere maintenance role; this is a
      specialized, partly kinase-independent activity rather than the primary function.
    supported_by:
    - reference_id: PMID:20140190
      supporting_text: >-
        the Rad3(ATR)-Rad26(ATRIP) complex contributes to the recruitment of Tel1(ATM)
        independently of Rad3(ATR) kinase activity
      reference_section_type: ABSTRACT
- term:
    id: GO:0140445
    label: chromosome, telomeric repeat region
  evidence_type: IDA
  original_reference_id: PMID:20140190
  qualifier: is_active_in
  review:
    summary: >-
      Supported. Rad3 (with Rad26) associates with telomeric repeat DNA, where it acts in
      telomere maintenance.
    action: ACCEPT
    reason: ChIP evidence of Rad3-Rad26 telomere association.
    supported_by:
    - reference_id: PMID:20140190
      supporting_text: >-
        both wild-type Rad3ATR and Rad3-kdΔATR proteins associate with telomeric DNA in a
        Rad26-dependent manner
      reference_section_type: RESULTS
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21084840
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 (and/or Tel1) phosphorylates the meiotic kinase Mek1 at S12/S14/T15 in
      response to programmed meiotic double-strand breaks.
    action: ACCEPT
    reason: Direct evidence of Rad3-dependent Mek1 phosphorylation.
    supported_by:
    - reference_id: PMID:21084840
      supporting_text: >-
        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)
      reference_section_type: ABSTRACT
- term:
    id: GO:1904514
    label: positive regulation of initiation of premeiotic DNA replication
  evidence_type: IMP
  original_reference_id: PMID:21084840
  qualifier: involved_in
  review:
    summary: >-
      The Rad3-Cds1 pathway coordinates the initiation of meiotic recombination and meiotic
      divisions with premeiotic DNA synthesis, and Mek1-T15 phosphorylation is important for
      meiotic S phase. This is a peripheral, meiosis-specific role rather than a core
      function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supported as a meiosis-specific regulatory role, but secondary to Rad3's core
      checkpoint-kinase function.
    supported_by:
    - reference_id: PMID:21084840
      supporting_text: >-
        Rad3-Cds1 pathway coordinates the initiation of meiotic recombination and meiotic
        cell divisions with premeiotic DNA synthesis.
      reference_section_type: INTRODUCTION
- term:
    id: GO:0000723
    label: telomere maintenance
  evidence_type: IMP
  original_reference_id: PMID:12196391
  qualifier: involved_in
  review:
    summary: >-
      Supported. Rad3/Rad26 is one of two redundant pathways (with Tel1/Rad32) required to
      maintain telomeres and prevent chromosome circularization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Well-supported telomere maintenance role; a specialized activity rather than the core
      checkpoint-signaling function.
    supported_by:
    - reference_id: PMID:12196391
      supporting_text: >-
        Rad3/Rad26 and Tel1/Rad32 represent two pathways required to maintain telomeres and
        prevent chromosome circularization
      reference_section_type: ABSTRACT
- term:
    id: GO:0140445
    label: chromosome, telomeric repeat region
  evidence_type: IDA
  original_reference_id: PMID:12196391
  qualifier: is_active_in
  review:
    summary: >-
      Supported. ChIP shows Rad3 associates with telomeres, where it contributes to telomere
      maintenance and protection.
    action: ACCEPT
    reason: Direct ChIP evidence of Rad3 telomere association.
    supported_by:
    - reference_id: PMID:12196391
      supporting_text: >-
        Chromatin immunoprecipitation analyses found that Rad3, Rad1, Rad9, Hus1, Rad17,
        Rad32, and Ku70 associate with telomeres.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11553781
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 directly phosphorylates the effector kinase Chk1 at Ser-345, the
      key event in DNA damage checkpoint signal transduction.
    action: ACCEPT
    reason: Direct evidence of Rad3-dependent Chk1 Ser-345 phosphorylation.
    supported_by:
    - reference_id: PMID:11553781
      supporting_text: >-
        Rad3 and ATM phosphorylate serine-345 of fission yeast Chk1. Mutation of serine-345
        (chk1-S345A) abrogates Rad3-dependent phosphorylation of Chk1 in vivo.
      reference_section_type: ABSTRACT
- term:
    id: GO:0033314
    label: mitotic DNA replication checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:11313465
  qualifier: involved_in
  review:
    summary: >-
      Core biological process. Rad3 is the upstream kinase of the replication checkpoint;
      it phosphorylates Cds1 (T11) to enforce the S-M checkpoint coupling mitosis to
      completion of DNA synthesis.
    action: ACCEPT
    reason: Direct evidence that Rad3-dependent Cds1 activation enforces the S-M checkpoint.
    supported_by:
    - reference_id: PMID:11313465
      supporting_text: >-
        Rad3-dependent phosphorylation of Cds1 at threonine-11 is required for Cds1
        activation and function.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11313465
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 phosphorylates Cds1 at Thr-11 (T11Q12 motif) in vitro, required for Cds1
      activation.
    action: ACCEPT
    reason: Direct in vitro evidence of Rad3-dependent Cds1 phosphorylation.
    supported_by:
    - reference_id: PMID:11313465
      supporting_text: >-
        Rad3 and ATM phosphorylate the N-terminal domain of Cds1 at the motif T(11)Q(12).
      reference_section_type: ABSTRACT
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:21945095
  qualifier: is_active_in
  review:
    summary: >-
      Supported. Rad3 acts on chromatin at replication origins, consistent with its
      replication-checkpoint surveillance function (Mcm10/Rad4-Cut5/TopBP1 context).
    action: ACCEPT
    reason: Consistent with chromatin localization at origins/forks.
    supported_by:
    - reference_id: PMID:17531813
      supporting_text: >-
        Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3
        and Rad26.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21099360
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 acts via the Rad3-Mrc1 (Claspin) pathway to activate Cds1 in response to
      replication stress.
    action: ACCEPT
    reason: Consistent with Rad3's established replication-checkpoint kinase activity.
    supported_by:
    - reference_id: PMID:16618806
      supporting_text: >-
        Activation of Cds1 is known to require the upstream kinase Rad3 and the mediator
        Mrc1
      reference_section_type: ABSTRACT
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:18180284
  qualifier: is_active_in
  review:
    summary: >-
      Nucleolar localization is weakly supported and likely a minor or context-specific
      pool. Rad3's well-established sites of action are chromatin, stalled forks and
      telomeres, not the nucleolus.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      A single localization observation; not a core functional site and not the principal
      compartment for Rad3 checkpoint activity.
    supported_by:
    - reference_id: PMID:17531813
      supporting_text: >-
        Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3
        and Rad26.
      reference_section_type: ABSTRACT
- term:
    id: GO:0044773
    label: mitotic DNA damage checkpoint signaling
  evidence_type: EXP
  original_reference_id: PMID:15226425
  qualifier: involved_in
  review:
    summary: >-
      Core BP. Rad3 (with Tel1) mediates the DNA-damage checkpoint via gamma-H2A formation,
      Crb2 recruitment and checkpoint maintenance after DNA breaks.
    action: ACCEPT
    reason: >-
      Experimental evidence that Rad3-dependent gamma-H2A maintains checkpoint arrest after
      damage.
    supported_by:
    - reference_id: PMID:15226425
      supporting_text: >-
        Mutation of the SQE motif to AQE (H2A-AQE) in the two histone H2A genes caused
        sensitivity to a wide range of genotoxic agents, increased spontaneous DNA damage,
        and impaired checkpoint maintenance.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031573
    label: mitotic intra-S DNA damage checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:19037101
  qualifier: involved_in
  review:
    summary: >-
      Core BP. Rad3 is required for the S-phase DNA damage checkpoint; the Mus81/Rhp51/Rqh1
      pathway acts in this Rad3/Cds1-dependent response.
    action: ACCEPT
    reason: Genetic evidence places rad3 in the S-phase DNA damage checkpoint.
    supported_by:
    - reference_id: PMID:12032307
      supporting_text: >-
        The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1,
        and on Rad4/Cut5
      reference_section_type: ABSTRACT
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IMP
  original_reference_id: PMID:1594599
  qualifier: involved_in
  review:
    summary: >-
      Rad3 contributes to DNA repair, but largely indirectly through checkpoint signaling
      that licenses and coordinates repair (e.g. via gamma-H2A and Crb2 recruitment) rather
      than acting as a direct repair enzyme.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supported but indirect; the core function is checkpoint signaling, which in turn
      influences repair.
    supported_by:
    - reference_id: PMID:1594599
      supporting_text: >-
        The rad3+ gene is also likely to play a role in DNA repair.
      reference_section_type: ABSTRACT
- term:
    id: GO:0007095
    label: mitotic G2 DNA damage checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:1594599
  qualifier: involved_in
  review:
    summary: >-
      Core BP. rad3 mutants fail to arrest in G2 after gamma-irradiation, defining Rad3 as
      essential for the G2 DNA damage checkpoint.
    action: ACCEPT
    reason: Classic genetic evidence for the G2 DNA damage checkpoint defect.
    supported_by:
    - reference_id: PMID:1594599
      supporting_text: >-
        the mutant cells are unable to arrest in the G2 phase of the cell cycle after DNA
        damage by gamma-irradiation
      reference_section_type: ABSTRACT
- term:
    id: GO:0031573
    label: mitotic intra-S DNA damage checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:1594599
  qualifier: involved_in
  review:
    summary: >-
      Core BP. Rad3 is required to maintain the dependence of mitosis on completion of DNA
      synthesis, i.e. the intra-S/replication-coupled checkpoint.
    action: ACCEPT
    reason: Genetic evidence of S-phase checkpoint defect in rad3 mutants.
    supported_by:
    - reference_id: PMID:1594599
      supporting_text: >-
        incapable of maintaining the dependence of mitosis upon the completion of DNA
        synthesis
      reference_section_type: ABSTRACT
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IMP
  original_reference_id: PMID:22302936
  qualifier: enables
  review:
    summary: >-
      Correct but general. Rad3 phosphorylates the telomere protein Ccq1 (Thr-93); the
      specific protein Ser/Thr kinase term is preferred.
    action: MODIFY
    reason: Rad3 is a protein Ser/Thr kinase; the more specific term should be used.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    supported_by:
    - reference_id: PMID:22302936
      supporting_text: >-
        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
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:10512862
  qualifier: enables
  review:
    summary: >-
      Core MF. Rad3 has protein kinase activity; the conserved kinase domain is necessary
      (though not sufficient) for catalytic activity and checkpoint function.
    action: ACCEPT
    reason: >-
      Biochemical/genetic evidence on Rad3 catalytic activity and the requirement of the
      kinase domain.
    supported_by:
    - reference_id: PMID:10512862
      supporting_text: >-
        these sequences are required for catalytic activity
      reference_section_type: DISCUSSION
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:16823372
  qualifier: is_active_in
  review:
    summary: >-
      Cytosol derives from a high-throughput ORFeome localization screen and conflicts with
      the strongly supported nuclear/chromatin/telomere localization where Rad3 acts. Rad3
      is not active in the cytosol.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput localization is non-specific; the functional site of Rad3 is the
      nucleus/chromatin, not the cytosol.
    supported_by:
    - reference_id: PMID:16823372
      supporting_text: >-
        ORFeome cloning and global analysis of protein localization in the fission yeast
        Schizosaccharomyces pombe.
      reference_section_type: TITLE
- term:
    id: GO:0031573
    label: mitotic intra-S DNA damage checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:12032307
  qualifier: involved_in
  review:
    summary: >-
      Core BP. The intra-S-phase checkpoint that slows DNA synthesis when forks encounter
      damage depends on the checkpoint-Rad proteins including Rad3.
    action: ACCEPT
    reason: Genetic evidence that the intra-S checkpoint requires the checkpoint-Rad proteins.
    supported_by:
    - reference_id: PMID:12032307
      supporting_text: >-
        The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1,
        and on Rad4/Cut5
      reference_section_type: ABSTRACT
- term:
    id: GO:0000228
    label: nuclear chromosome
  evidence_type: IDA
  original_reference_id: PMID:8843195
  qualifier: is_active_in
  review:
    summary: >-
      Association with (meiotic) nuclear chromosomes is consistent with Rad3 acting on
      chromatin, but the cited study primarily characterized the mammalian Atr/Atm orthologs
      on meiotic chromosomes; for S. pombe Rad3 this is supported by analogy and by direct
      pombe chromatin/telomere ChIP in other studies.
    action: KEEP_AS_NON_CORE
    reason: >-
      Compartment is plausible and corroborated by pombe chromatin localization, but the
      specific cited evidence is largely from orthologs; the generic chromatin/chromosome
      terms already cover the core site.
    supported_by:
    - reference_id: PMID:8843195
      supporting_text: >-
        Atr is found at sites along unpaired or asynapsed chromosomal axes
      reference_section_type: ABSTRACT
core_functions:
- description: >-
    Apical sensor protein serine/threonine kinase of the DNA-structure checkpoints that
    phosphorylates SQ/TQ motifs in checkpoint substrates to transduce DNA damage and
    replication-stress signals.
  supported_by:
  - reference_id: PMID:11553781
    supporting_text: >-
      Rad3 and ATM phosphorylate serine-345 of fission yeast Chk1.
    reference_section_type: ABSTRACT
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0000077
    label: DNA damage checkpoint signaling
  in_complex:
    id: GO:0070310
    label: ATR-ATRIP complex
- description: >-
    Activates the effector kinase Chk1 by direct phosphorylation (Ser-345) to enforce the
    G2/M DNA damage checkpoint, delaying mitosis after DNA damage.
  supported_by:
  - reference_id: PMID:11553781
    supporting_text: >-
      Mutation of serine-345 (chk1-S345A) abrogates Rad3-dependent phosphorylation of Chk1
      in vivo. The chk1-S345A cells are sensitive to DNA damage and are checkpoint defective.
    reference_section_type: ABSTRACT
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0007095
    label: mitotic G2 DNA damage checkpoint signaling
- description: >-
    Activates the effector kinase Cds1 (via Cds1-T11 and the mediator Mrc1) to enforce the
    DNA replication checkpoint that couples mitosis to completion of DNA synthesis.
  supported_by:
  - reference_id: PMID:11313465
    supporting_text: >-
      Rad3-dependent phosphorylation of Cds1 at threonine-11 is required for Cds1 activation
      and function.
    reference_section_type: ABSTRACT
  - reference_id: PMID:14585996
    supporting_text: >-
      Mrc1 (mediator of replication checkpoint 1) is an adaptor checkpoint protein required
      for Rad3-dependent activation of the checkpoint kinase Cds1 in response to arrest of
      replication forks.
    reference_section_type: ABSTRACT
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0033314
    label: mitotic DNA replication checkpoint signaling
- description: >-
    Phosphorylates histone H2A (generating gamma-H2A) redundantly with Tel1 at sites of DNA
    damage to recruit the mediator Crb2 and maintain checkpoint arrest.
  supported_by:
  - reference_id: PMID:15226425
    supporting_text: >-
      formation of gamma-H2A redundantly requires the ATR/ATM-related kinases Rad3 and Tel1
    reference_section_type: ABSTRACT
  molecular_function:
    id: GO:0140995
    label: histone H2A kinase activity
  directly_involved_in:
  - id: GO:0044773
    label: mitotic DNA damage checkpoint signaling
proposed_new_terms: []
suggested_questions:
- question: >-
    Which Rad3 substrate phosphorylations are direct in vivo versus dependent on additional
    mediators (Crb2, Mrc1, 9-1-1 clamp), and how is substrate selectivity between the Chk1
    (damage) and Cds1 (replication) branches achieved?
- question: >-
    What is the molecular basis of the kinase-independent functions of the Rad3-Rad26
    complex (e.g. Tel1 recruitment to telomeres), and how widespread are such structural
    roles?
suggested_experiments:
- description: >-
    Analog-sensitive (as) rad3 kinase allele combined with quantitative phosphoproteomics
    to define the in vivo Rad3-dependent SQ/TQ phosphoproteome during DNA damage versus
    replication stress.
- description: >-
    Separation-of-function rad3 alleles (kinase-dead vs scaffold-defective) to dissect
    catalytic versus structural contributions of the Rad3-Rad26 complex in checkpoint
    signaling and telomere maintenance.
references:
- id: file:interpro/panther/PTHR11139/PTHR11139-review.md
  title: 'PANTHER family review PTHR11139: IBA propagation assessment for rad3'
  findings: []
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10512862
  title: Requirement of sequences outside the conserved kinase domain of fission yeast Rad3p for checkpoint control.
  findings:
  - statement: >-
      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.
    supporting_text: >-
      Despite this similarity, none of the PI3-kinase-related (PI3KR) proteins have been
      shown to phosphorylate lipids.
    reference_section_type: INTRODUCTION
- id: PMID:10521402
  title: Meiotic DNA replication checkpoint control in fission yeast.
  findings:
  - statement: >-
      The meiotic DNA replication checkpoint requires the mitotic checkpoint Rad genes
      (including rad3) and Cds1.
    supporting_text: >-
      The mitotic checkpoint Rad genes and the Cds1 protein kinase are required for the DNA
      replication checkpoint during meiosis
    reference_section_type: ABSTRACT
- id: PMID:10559981
  title: A Rad3-Rad26 complex responds to DNA damage independently of other checkpoint proteins.
  findings:
  - statement: >-
      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.
    supporting_text: >-
      Here we report a stable association between Rad3 and Rad26 in soluble protein extracts.
      Rad26 shows Rad3-dependent phosphorylation after DNA damage.
    reference_section_type: ABSTRACT
- id: PMID:11313465
  title: Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation of fission yeast checkpoint kinase Cds1.
  findings:
  - statement: Rad3 phosphorylates Cds1 at Thr-11 (T11Q12), required for Cds1 activation and the S-M checkpoint.
    supporting_text: >-
      Rad3-dependent phosphorylation of Cds1 at threonine-11 is required for Cds1 activation
      and function.
    reference_section_type: ABSTRACT
- id: PMID:11553781
  title: Serine-345 is required for Rad3-dependent phosphorylation and function of checkpoint kinase Chk1 in fission yeast.
  findings:
  - statement: Rad3 directly phosphorylates Chk1 at Ser-345, required for the G2/M DNA damage checkpoint.
    supporting_text: >-
      Rad3 and ATM phosphorylate serine-345 of fission yeast Chk1. Mutation of serine-345
      (chk1-S345A) abrogates Rad3-dependent phosphorylation of Chk1 in vivo.
    reference_section_type: ABSTRACT
- id: PMID:12032307
  title: A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway.
  findings:
  - statement: >-
      The intra-S-phase checkpoint that slows DNA synthesis requires the checkpoint-Rad
      proteins and Cds1 and is triggered when forks encounter damage.
    supporting_text: >-
      The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1,
      and on Rad4/Cut5
    reference_section_type: ABSTRACT
- id: PMID:12196391
  title: Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres.
  findings:
  - statement: >-
      Rad3/Rad26 and Tel1/Rad32 are two redundant pathways required to maintain telomeres
      and prevent chromosome circularization; Rad3 associates with telomeres.
    supporting_text: >-
      Rad3/Rad26 and Tel1/Rad32 represent two pathways required to maintain telomeres and
      prevent chromosome circularization
    reference_section_type: ABSTRACT
- id: PMID:14585996
  title: Replication checkpoint protein Mrc1 is regulated by Rad3 and Tel1 in fission yeast.
  findings:
  - statement: Rad3 (with Tel1) phosphorylates the mediator Mrc1 at S/TQ motifs to control Cds1.
    supporting_text: >-
      Rad3 and Tel1 regulate Mrc1 through differential phosphorylation to control Cds1.
    reference_section_type: ABSTRACT
- id: PMID:14739927
  title: Regulation of checkpoint kinases through dynamic interaction with Crb2.
  findings:
  - statement: >-
      Rad3 interacts directly with the mediator Crb2 and regulates Chk1 activation through
      dynamic Rad3-Crb2-Chk1 interactions.
    supporting_text: >-
      we show direct interaction between Rad3 and Crb2, which is inhibitory to Rad3 activity.
    reference_section_type: ABSTRACT
- id: PMID:15155581
  title: Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1.
  findings:
  - statement: Rad3 phosphorylates the 9-1-1 clamp subunit Rad9 at T412/S423 to enable Chk1 activation.
    supporting_text: >-
      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
    reference_section_type: ABSTRACT
- id: PMID:15226425
  title: Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast.
  findings:
  - statement: Rad3 and Tel1 redundantly phosphorylate histone H2A (gamma-H2A) to recruit Crb2 and maintain checkpoint arrest.
    supporting_text: >-
      formation of gamma-H2A redundantly requires the ATR/ATM-related kinases Rad3 and Tel1
    reference_section_type: ABSTRACT
- id: PMID:1594599
  title: The rad3+ gene of Schizosaccharomyces pombe is involved in multiple checkpoint functions and in DNA repair.
  findings:
  - statement: >-
      rad3 mutants fail G2 arrest after irradiation and fail to couple mitosis to completion
      of DNA synthesis; rad3 also contributes to DNA repair.
    supporting_text: >-
      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
    reference_section_type: ABSTRACT
- id: PMID:16618806
  title: Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast.
  findings:
  - statement: >-
      Cds1 is recruited by Mrc1 to stalled forks and primed by Rad3-dependent
      phosphorylation, then activated by FHA-mediated dimerization and autophosphorylation.
    supporting_text: >-
      Cds1 is then primed for activation by Rad3-dependent phosphorylation.
    reference_section_type: ABSTRACT
- id: PMID:16823372
  title: ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
  findings:
  - statement: High-throughput localization screen reporting a cytosol signal for Rad3 (low specificity).
    supporting_text: >-
      ORFeome cloning and global analysis of protein localization in the fission yeast
      Schizosaccharomyces pombe.
    reference_section_type: TITLE
- id: PMID:17531813
  title: Cdc18 enforces long-term maintenance of the S phase checkpoint by anchoring the Rad3-Rad26 complex to chromatin.
  findings:
  - statement: Cdc18 anchors the Rad3-Rad26 complex to chromatin during stalled replication for long-term S-phase checkpoint maintenance.
    supporting_text: >-
      Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3 and
      Rad26.
    reference_section_type: ABSTRACT
- id: PMID:18180284
  title: Minichromosome maintenance proteins interact with checkpoint and recombination proteins to promote s-phase genome stability.
  findings:
  - statement: MCM proteins interact with checkpoint/recombination proteins; reports a nucleolar Rad3 localization.
    supporting_text: >-
      Minichromosome maintenance proteins interact with checkpoint and recombination
      proteins to promote s-phase genome stability.
    reference_section_type: TITLE
- id: PMID:19037101
  title: Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint.
  findings:
  - statement: Mus81/Rhp51/Rqh1 act in an epistatic pathway required for the S-phase DNA damage checkpoint with Rad3/Cds1.
    supporting_text: >-
      Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA
      damage checkpoint.
    reference_section_type: TITLE
- id: PMID:20140190
  title: A kinase-independent role for the Rad3(ATR)-Rad26(ATRIP) complex in recruitment of Tel1(ATM) to telomeres in fission yeast.
  findings:
  - statement: >-
      The Rad3-Rad26 complex recruits Tel1 to telomeres independently of Rad3 kinase
      activity; Rad26 is required for Rad3 telomere association.
    supporting_text: >-
      the Rad3(ATR)-Rad26(ATRIP) complex contributes to the recruitment of Tel1(ATM)
      independently of Rad3(ATR) kinase activity
    reference_section_type: ABSTRACT
- id: PMID:21084840
  title: The Mek1 phosphorylation cascade plays a role in meiotic recombination of Schizosaccharomyces pombe.
  findings:
  - statement: Rad3 (and/or Tel1) phosphorylates the meiotic kinase Mek1 at S12/S14/T15 in response to meiotic DSBs.
    supporting_text: >-
      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)
    reference_section_type: ABSTRACT
- id: PMID:21099360
  title: Hsk1 kinase and Cdc45 regulate replication stress-induced checkpoint responses in fission yeast.
  findings:
  - statement: Hsk1 and Cdc45 regulate replication-stress checkpoint responses acting with the Rad3-Mrc1 pathway to activate Cds1.
    supporting_text: >-
      Hsk1 kinase and Cdc45 regulate replication stress-induced checkpoint responses in
      fission yeast.
    reference_section_type: TITLE
- id: PMID:21945095
  title: Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1).
  findings:
  - statement: Mcm10 interacts with Rad4/Cut5(TopBP1) at replication origins, the chromatin context where Rad3 surveys replication.
    supporting_text: >-
      Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA
      replication is dependent on Rad4/Cut5(TopBP1).
    reference_section_type: TITLE
- id: PMID:22302936
  title: Tel1(ATM) and Rad3(ATR) phosphorylate the telomere protein Ccq1 to recruit telomerase and elongate telomeres in fission yeast.
  findings:
  - statement: Rad3 (with Tel1) phosphorylates Ccq1 at Thr-93 to recruit telomerase and elongate telomeres.
    supporting_text: >-
      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
    reference_section_type: ABSTRACT
- id: PMID:29123917
  title: The telomere bouquet facilitates meiotic prophase progression and exit in fission yeast.
  findings:
  - statement: Persistent meiotic recombination damage activates the Rad3-Chk1 checkpoint, extending the meiotic prophase bouquet stage.
    supporting_text: >-
      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.
    reference_section_type: ABSTRACT
- id: PMID:8843195
  title: The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes.
  findings:
  - statement: >-
      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.
    supporting_text: >-
      Atr is found at sites along unpaired or asynapsed chromosomal axes
    reference_section_type: ABSTRACT
- id: PMID:8978690
  title: The Schizosaccharomyces pombe rad3 checkpoint gene.
  findings:
  - statement: >-
      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.
    supporting_text: >-
      immunoprecipitation of overexpressed Rad3 demonstrates an associated protein kinase
      activity
    reference_section_type: ABSTRACT