NCU02539 encodes the Mcm4 subunit of the conserved Mcm2-7 replicative helicase. Mcm4 contributes to DNA binding and ATP-dependent DNA unwinding in a multisubunit complex, participating in origin licensing, initiation and elongation of nuclear DNA replication. Its domain architecture includes the MCM N-terminal and OB-fold regions, an AAA+ ATPase domain and an Mcm4 winged-helix region.
Existing Annotations Review
GO Term
Evidence
Action
Reason
GO:0000727 double-strand break repair via break-induced replication
IBA GO_REF:0000033
KEEP AS NON CORE
Summary: Break-induced replication uses replication machinery for repair-associated DNA synthesis.
Reason: Break-induced replication uses replication machinery for repair-associated DNA synthesis. The curated Mcm4 phylogenetic inference supports this secondary application of the helicase, while ordinary nuclear genome replication remains the defining function.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex.
GO:0000727 double-strand break repair via break-induced replication
IEA GO_REF:0000107
KEEP AS NON CORE
Summary: Break-induced replication uses replication machinery for repair-associated DNA synthesis.
Reason: Break-induced replication uses replication machinery for repair-associated DNA synthesis. The curated Mcm4 phylogenetic inference supports this secondary application of the helicase, while ordinary nuclear genome replication remains the defining function.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4 is a conserved nuclear replicative helicase subunit.
Reason: Mcm4 is a conserved nuclear replicative helicase subunit. Mcm2-7 complexes are loaded onto chromosomal DNA during origin licensing, supporting nuclear and chromatin association of the target by family-based inference.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4 is a conserved nuclear replicative helicase subunit.
Reason: Mcm4 is a conserved nuclear replicative helicase subunit. Mcm2-7 complexes are loaded onto chromosomal DNA during origin licensing, supporting nuclear and chromatin association of the target by family-based inference.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1.
Reason: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1. Conservation of the Mcm4 subunit supports participation in prereplicative and preinitiation assemblies and association with replication origins, without assigning origin sequence recognition to Mcm4 alone.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The ortholog transfer specifies RNA binding or DNA/RNA hybrid helicase activity.
Reason: The ortholog transfer specifies RNA binding or DNA/RNA hybrid helicase activity. The inspected Mcm4 experiments establish a DNA helicase complex, but do not resolve physiological RNA-substrate activity or its conservation in Neurospora. This added substrate specificity remains uncertain.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4 AAA+ domain retains annotated Walker A and Walker B nucleotide-binding regions, supporting an ATPase contribution to the MCM motor.
Reason: The Mcm4 AAA+ domain retains annotated Walker A and Walker B nucleotide-binding regions, supporting an ATPase contribution to the MCM motor. The PROSITE caution about unspecified missing feature-propagation residues does not establish loss of the ATPase; the exact catalytic rate of isolated Neurospora Mcm4 is unmeasured.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4 is a conserved nuclear replicative helicase subunit.
Reason: Mcm4 is a conserved nuclear replicative helicase subunit. Mcm2-7 complexes are loaded onto chromosomal DNA during origin licensing, supporting nuclear and chromatin association of the target by family-based inference.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4 is a conserved nuclear replicative helicase subunit.
Reason: Mcm4 is a conserved nuclear replicative helicase subunit. Mcm2-7 complexes are loaded onto chromosomal DNA during origin licensing, supporting nuclear and chromatin association of the target by family-based inference.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1.
Reason: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1. Conservation of the Mcm4 subunit supports participation in prereplicative and preinitiation assemblies and association with replication origins, without assigning origin sequence recognition to Mcm4 alone.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: A cytoplasmic pool is compatible with regulated nucleocytoplasmic distribution of MCM proteins and the ortholog-derived localization.
Reason: A cytoplasmic pool is compatible with regulated nucleocytoplasmic distribution of MCM proteins and the ortholog-derived localization. The DNA-replication function is nuclear, so the broader cellular pool is retained as non-core.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4 subfamily is a core component of the nuclear replication helicase.
Reason: The Mcm4 subfamily is a core component of the nuclear replication helicase. Conserved Mcm2-7 loading and activation establish its involvement in licensing and replication initiation, including the mitotic cell cycle.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex.
GO:0006267 pre-replicative complex assembly involved in nuclear cell cycle DNA replication
IEA GO_REF:0000107
ACCEPT
Summary: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1.
Reason: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1. Conservation of the Mcm4 subunit supports participation in prereplicative and preinitiation assemblies and association with replication origins, without assigning origin sequence recognition to Mcm4 alone.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4 subfamily is a core component of the nuclear replication helicase.
Reason: The Mcm4 subfamily is a core component of the nuclear replication helicase. Conserved Mcm2-7 loading and activation establish its involvement in licensing and replication initiation, including the mitotic cell cycle.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex.
GO:0006271 DNA strand elongation involved in DNA replication
IBA GO_REF:0000033
ACCEPT
Summary: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks.
Reason: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks. Thus DNA strand elongation and nuclear replication fork/CMG association are conserved subunit functions, not merely consequences of a replication phenotype.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex.
GO:0006271 DNA strand elongation involved in DNA replication
IEA GO_REF:0000107
ACCEPT
Summary: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks.
Reason: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks. Thus DNA strand elongation and nuclear replication fork/CMG association are conserved subunit functions, not merely consequences of a replication phenotype.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Premeiotic replication uses the conserved Mcm2-7 helicase machinery.
Reason: Premeiotic replication uses the conserved Mcm2-7 helicase machinery. This developmental context is compatible with Mcm4 function, but its specific regulation during Neurospora sexual development has not been established here.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Four-way junction helicase activity is a particular substrate geometry beyond the demonstrated replicative DNA-unwinding role.
Reason: Four-way junction helicase activity is a particular substrate geometry beyond the demonstrated replicative DNA-unwinding role. The electronic ortholog transfer was not traced to a conserved target-relevant assay, so this biochemical specificity remains unresolved.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4 AAA+ domain retains annotated Walker A and Walker B nucleotide-binding regions, supporting an ATPase contribution to the MCM motor.
Reason: The Mcm4 AAA+ domain retains annotated Walker A and Walker B nucleotide-binding regions, supporting an ATPase contribution to the MCM motor. The PROSITE caution about unspecified missing feature-propagation residues does not establish loss of the ATPase; the exact catalytic rate of isolated Neurospora Mcm4 is unmeasured.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The rDNA protrusion is a specific nuclear structure, not interchangeable with general chromatin or replication fork localization.
Reason: The rDNA protrusion is a specific nuclear structure, not interchangeable with general chromatin or replication fork localization. The transferred fission-yeast subcompartment assignment needs evidence that the structure and Mcm4 residence are conserved in Neurospora.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1.
Reason: Purified budding-yeast Mcm2-7 is recruited and loaded onto origin DNA by ORC, Cdc6 and Cdt1. Conservation of the Mcm4 subunit supports participation in prereplicative and preinitiation assemblies and association with replication origins, without assigning origin sequence recognition to Mcm4 alone.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4 subfamily is a core component of the nuclear replication helicase.
Reason: The Mcm4 subfamily is a core component of the nuclear replication helicase. Conserved Mcm2-7 loading and activation establish its involvement in licensing and replication initiation, including the mitotic cell cycle.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The ortholog transfer specifies RNA binding or DNA/RNA hybrid helicase activity.
Reason: The ortholog transfer specifies RNA binding or DNA/RNA hybrid helicase activity. The inspected Mcm4 experiments establish a DNA helicase complex, but do not resolve physiological RNA-substrate activity or its conservation in Neurospora. This added substrate specificity remains uncertain.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4-specific family assignment and conserved MCM domain architecture support membership in the Mcm2-7 core helicase complex.
Reason: The Mcm4-specific family assignment and conserved MCM domain architecture support membership in the Mcm2-7 core helicase complex. Biochemical reconstitution directly establishes the homologous multisubunit assembly.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4-specific family assignment and conserved MCM domain architecture support membership in the Mcm2-7 core helicase complex.
Reason: The Mcm4-specific family assignment and conserved MCM domain architecture support membership in the Mcm2-7 core helicase complex. Biochemical reconstitution directly establishes the homologous multisubunit assembly.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks.
Reason: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks. Thus DNA strand elongation and nuclear replication fork/CMG association are conserved subunit functions, not merely consequences of a replication phenotype.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks.
Reason: Mcm4 remains part of the MCM motor in the Cdc45–MCM–GINS helicase at progressing replication forks. Thus DNA strand elongation and nuclear replication fork/CMG association are conserved subunit functions, not merely consequences of a replication phenotype.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4-specific family assignment and conserved MCM domain architecture support membership in the Mcm2-7 core helicase complex.
Reason: The Mcm4-specific family assignment and conserved MCM domain architecture support membership in the Mcm2-7 core helicase complex. Biochemical reconstitution directly establishes the homologous multisubunit assembly.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
Summary: The Mcm4 subfamily is a core component of the nuclear replication helicase.
Reason: The Mcm4 subfamily is a core component of the nuclear replication helicase. Conserved Mcm2-7 loading and activation establish its involvement in licensing and replication initiation, including the mitotic cell cycle.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex.
GO:1990518 single-stranded 3'-5' DNA helicase activity
IEA GO_REF:0000107
ACCEPT
Summary: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit.
Reason: Mcm4-specific InterPro and PANTHER assignments and the MCM domain architecture identify a replicative helicase subunit. Reconstitution and mutant analysis of Mcm4-containing complexes support DNA binding and 3′–5′ DNA unwinding; the activity is executed by the assembled helicase, not an isolated Mcm4 monomer.
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs).
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Review rationale: InterPro MCM_4 and the Mcm4-specific PANTHER assignment identify a conserved replicative helicase subunit. Reconstitution of Mcm2-7 origin loading and biochemical study of Mcm4-containing complexes support participation in nuclear DNA replication. GOA already includes the more specific mitotic DNA replication initiation and DNA strand elongation functions. The broad prediction is therefore less precise; its hydration from premeiotic replication is provenance rather than independent evidence for a Neurospora meiotic assay.
PMID:19896182: "The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs)."
PMID:10567526: "the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex."
Review rationale: The Mcm4-specific sequence assignment supports membership in the Mcm2-7 helicase. Purified budding-yeast Mcm2-7 loading establishes the conserved role in origin licensing, a prerequisite for initiation. The existing curated phylogenetic annotation specifies mitotic DNA replication initiation, making the generic initiation prediction less precise. The judgment concerns participation of the Mcm4 subunit in the complex, not autonomous initiation activity.
PMID:19896182: "The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs)."
PMID:10567526: "the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex."
Review rationale: The target has the Mcm4-specific MCM domain architecture, including an OB-fold DNA-associated region. Biochemical analysis of Mcm4-containing complexes supports a contribution to single-stranded DNA binding, which is already annotated through PAINT. The generic DNA-binding prediction loses that substrate specificity. Binding and helicase activity are properties of the assembled MCM machinery, not evidence for an independent monomeric DNA-binding regulator.
PMID:19896182: "The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs)."
PMID:10567526: "the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex."