MSI1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000786 nucleosome	IDA PMID:30239791 Mechanistic insights into histone deposition and nucleosome ...	REMOVE	Summary: Complex Portal annotation placing MSI1 (a CAF-1 subunit) as part_of the nucleosome, citing a review of CAF-1 mechanism (PMID:30239791). Reason: CAF-1 is a histone H3-H4 chaperone that deposits H3-H4 onto DNA to build the tetrasome; it is not a structural component of the nucleosome core particle, which consists of the histone octamer and DNA. The cited paper (full text cached; a review) describes CAF-1 binding a single H3-H4 dimer and depositing (H3-H4)2 tetramers onto nucleosome-free DNA, i.e. a transient assembly intermediate, not stable membership of the nucleosome. The part_of nucleosome claim is contradicted by the very source cited, so it is removed; the chaperone role is captured by GO:0006335 and CAF-1 complex membership (GO:0033186). Supporting Evidence: PMID:30239791 The Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the replisome and deposits H3-H4 directly onto newly synthesized DNA. PMID:30239791 Two CAF-1•H3-H4 complexes co-associate on nucleosome-free DNA depositing (H3-H4)2 tetramers in the first step of nucleosome assembly.
GO:0005515 protein binding	IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ...	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Rlf2/Cac1. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005515 protein binding	IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy...	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Rlf2/Cac1. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Cac2. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Rlf2/Cac1. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005515 protein binding	IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome.	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Rlf2/Cac1. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005515 protein binding	IPI PMID:21256037 Structure of the Rtt109-AcCoA/Vps75 complex and implications...	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Cac2. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Cac2. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	REMOVE	Summary: Generic protein binding (IPI) between MSI1 and Rlf2/Cac1. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. This is an interaction between subunits of the CAF-1 heterotrimer, which is captured informatively by part_of CAF-1 complex (GO:0033186).
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that MSI1 is active in the nucleus. Reason: CAF-1 acts on nuclear chromatin at replication forks; consistent with direct localization data. Supporting Evidence: PMID:30239791 It localizes to sites of ongoing DNA synthesis by binding to the processivity factor for DNA polymerases known as Proliferating cell nuclear antigen (PCNA)
GO:0005634 nucleus	IDA PMID:11238915 CAC3(MSI1) suppression of RAS2(G19V) is independent of chrom...	ACCEPT	Summary: Cac3p/Msi1p localizes to the nucleus (and cytoplasm). Reason: Nuclear pool is where Msi1 acts as a CAF-1 subunit. Supporting Evidence: PMID:11238915 Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping places MSI1 in the nucleus. Reason: Consistent with direct localization evidence and with CAF-1 function on nuclear chromatin.
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic inference placing MSI1 in the cytoplasm. Reason: Consistent with direct evidence that Cac3p/Msi1p is partly cytoplasmic; non-core relative to its nuclear CAF-1 role. Supporting Evidence: PMID:11238915 Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm.
GO:0005737 cytoplasm	IDA PMID:11238915 CAC3(MSI1) suppression of RAS2(G19V) is independent of chrom...	KEEP AS NON CORE	Summary: Cac3p/Msi1p localizes to the cytoplasm as well as the nucleus. Reason: Johnston et al. show that, unlike Cac1p, Cac3p is found in both nucleus and cytoplasm, and that overexpressed Cac3p suppresses RAS/cAMP signalling by associating with the cytoplasmic kinase Npr1p, independently of CAC1 and CAC2. The cytoplasmic pool is real but relates to a secondary, CAF-1-independent activity (abstract-only cache). Supporting Evidence: PMID:11238915 Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm. PMID:11238915 indicating that Cac3p has at least two distinct, separable functions, one in chromatin assembly and one in regulating RAS function file:yeast/MSI1/MSI1-deep-research-falcon.md The nuclear pool supports CAF-1/chromatin functions, while the cytoplasmic pool supports a separable nutrient-signaling role.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location mapping placing MSI1 in the cytoplasm. Reason: Consistent with direct evidence that Cac3p/Msi1p is partly cytoplasmic; non-core relative to its nuclear CAF-1 role. Supporting Evidence: PMID:11238915 Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm.
GO:0006260 DNA replication	NAS PMID:30239791 Mechanistic insights into histone deposition and nucleosome ...	MARK AS OVER ANNOTATED	Summary: Complex Portal NAS annotation of MSI1/CAF-1 to the broad process DNA replication. Reason: CAF-1 does not synthesize or duplicate DNA; it couples nucleosome assembly to replication fork progression through PCNA binding. The replication-coupled role is precisely described by GO:0006335 (DNA replication-dependent chromatin assembly), which is annotated with direct evidence. CAC genes are not essential for viability, and no DNA synthesis defect is reported for cac mutants, so the parent process DNA replication overstates the contribution. Supporting Evidence: PMID:30239791 The Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the replisome and deposits H3-H4 directly onto newly synthesized DNA. PMID:9030687 Genes encoding the CAF-I subunits (collectively referred to as CAC genes) are not essential for cell viability
GO:0006281 DNA repair	NAS PMID:30239791 Mechanistic insights into histone deposition and nucleosome ...	KEEP AS NON CORE	Summary: Complex Portal NAS annotation of MSI1/CAF-1 to DNA repair. Reason: Deletion of any CAC gene causes UV sensitivity, and cac1 deletion increases the UV sensitivity of mutants in every major repair epistasis group, consistent with CAF-1 restoring chromatin on repaired DNA (it assembles nucleosomes on templates undergoing nucleotide excision repair in vitro). CAF-1 is also required for resistance to double-strand-break agents, but it is not required for repair of the DNA per se. The contribution is chromatin restoration coupled to repair rather than a repair activity, so this is kept as a non-core, pleiotropic process. Supporting Evidence: PMID:9030687 deletion of any CAC gene causes an increase in sensitivity to ultraviolet radiation, without significantly increasing sensitivity to gamma rays PMID:9927445 these data suggest that CAF-I has a role in error-free postreplicative damage repair and may also have an auxiliary role in other repair mechanisms PMID:16143623 CAF-1 is not required for repair of the DNA per se or for DNA damage checkpoint function.
GO:0006325 chromatin organization	IDA PMID:30239791 Mechanistic insights into histone deposition and nucleosome ...	MODIFY	Summary: Complex Portal annotation of MSI1/CAF-1 to the general process chromatin organization. Reason: Correct but uninformative. CAF-1 organizes chromatin specifically by depositing newly synthesized H3-H4 onto replicating DNA; the specific child term GO:0006335 DNA replication-dependent chromatin assembly is the appropriate term and is already supported by direct evidence for this subunit. Proposed replacements: DNA replication-dependent chromatin assembly Supporting Evidence: PMID:30239791 The Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the replisome and deposits H3-H4 directly onto newly synthesized DNA.
GO:0006335 DNA replication-dependent chromatin assembly	IDA PMID:30239791 Mechanistic insights into histone deposition and nucleosome ...	ACCEPT	Summary: Complex Portal annotation of MSI1/CAF-1 to DNA replication-dependent chromatin assembly. Reason: This is the defining function of CAF-1: the complex is recruited to replication forks via PCNA and deposits H3-H4 onto newly synthesized DNA. The cited paper (full text) summarizes the structural and biochemical work on the yeast complex. Supporting Evidence: PMID:30239791 The Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the replisome and deposits H3-H4 directly onto newly synthesized DNA. PMID:30239791 Two CAF-1•H3-H4 complexes co-associate on nucleosome-free DNA depositing (H3-H4)2 tetramers in the first step of nucleosome assembly.
GO:0006335 DNA replication-dependent chromatin assembly	IDA PMID:9030687 Ultraviolet radiation sensitivity and reduction of telomeric...	ACCEPT	Summary: MSI1 is a subunit of yeast CAF-I purified by Kaufman et al. using an in vitro replication-coupled nucleosome assembly assay. Reason: Kaufman et al. purified yeast CAF-I as the activity that assembles nucleosomes onto DNA undergoing replication in vitro, and identified CAC1/RLF2, CAC2 and CAC3/MSI1 as the genes for its three subunits. This is the founding biochemical evidence for the core function. Supporting Evidence: PMID:9030687 we now report the purification of CAF-I from the budding yeast Saccharomyces cerevisiae PMID:9030687 The CAC1 and CAC2 (chromatin assembly complex) genes encode proteins similar to the p150 and p60 subunits of human CAF-I, respectively PMID:9030687 The gene encoding the p50 subunit of yeast CAF-I (CAC3) is similar to the human p48 CAF-I subunit and was identified previously as MSI1
GO:0006338 chromatin remodeling	IBA GO_REF:0000033	MODIFY	Summary: Phylogenetic inference that MSI1 is involved in chromatin remodeling. Reason: The IBA node covers the RbAp46/48-like WD40 proteins, whose members sit in many chromatin-modifying complexes. In budding yeast, Msi1's documented chromatin role is as the small subunit of CAF-1, and deletion of any CAC gene, including CAC3/MSI1, strongly reduces telomeric silencing. GO:0006338 is broad; the specific chromatin remodeling process that yeast Msi1 supports is subtelomeric heterochromatin formation (GO:0031509, a descendant of chromatin remodeling), through CAF-1-mediated histone deposition into silent chromatin. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000522733 · PTN000522733 SUPPORTS TRANSFER RbAp46/48-family chromatin role is conserved; for yeast Msi1 the specific process is CAF-1-dependent subtelomeric heterochromatin formation, a descendant of chromatin remodeling. Proposed replacements: subtelomeric heterochromatin formation Supporting Evidence: PMID:9030687 Deletion of CAC genes also strongly reduces silencing of genes adjacent to telomeric DNA PMID:11756556 we isolated a mutation that reduced binding to the Cac3p subunit and another that impaired binding to the DNA replication protein PCNA
GO:0006355 regulation of DNA-templated transcription	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic inference that MSI1 is involved in regulation of DNA-templated transcription. Reason: Msi1 influences transcription indirectly, by supporting CAF-1-dependent heterochromatic silencing at telomeres; it is not known to act as a transcriptional regulator in yeast. Metazoan orthologs (RbAp46/48) sit in NuRD, PRC2 and HDAC complexes, which is the source of this broad node-level assertion. Retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000522733 · PTN000522733 SUPPORTS TRANSFER Broad family-level assertion; in yeast the effect on transcription is indirect, via CAF-1-dependent silencing. Supporting Evidence: PMID:9030687 Deletion of CAC genes also strongly reduces silencing of genes adjacent to telomeric DNA
GO:0033186 CAF-1 complex	IDA PMID:9030687 Ultraviolet radiation sensitivity and reduction of telomeric...	ACCEPT	Summary: MSI1 identified as a subunit of purified yeast CAF-I. Reason: Direct purification and peptide sequencing of yeast CAF-I identified the three subunits encoded by CAC1 (RLF2), CAC2 and CAC3 (MSI1). The recombinant heterotrimer has since been reconstituted and characterized structurally. Supporting Evidence: PMID:9030687 we now report the purification of CAF-I from the budding yeast Saccharomyces cerevisiae PMID:9030687 The CAC1 and CAC2 (chromatin assembly complex) genes encode proteins similar to the p150 and p60 subunits of human CAF-I, respectively PMID:9030687 The gene encoding the p50 subunit of yeast CAF-I (CAC3) is similar to the human p48 CAF-I subunit and was identified previously as MSI1 PMID:28315525 Budding yeast CAF1 (yCAF1) is a heterotrimeric complex containing the Cac1, Cac2 and Cac3 subunits (Kaufman et al., 1997).
GO:0033186 CAF-1 complex	IPI PMID:30239791 Mechanistic insights into histone deposition and nucleosome ...	ACCEPT	Summary: Complex Portal annotation of MSI1 as a CAF-1 complex subunit. Reason: Consistent with the purification of yeast CAF-I and the reconstitution of the Cac1-Cac2-Cac3 heterotrimer. Supporting Evidence: PMID:28315525 Budding yeast CAF1 (yCAF1) is a heterotrimeric complex containing the Cac1, Cac2 and Cac3 subunits (Kaufman et al., 1997).
GO:0033698 Rpd3L complex	IBA GO_REF:0000033	REMOVE	Summary: Phylogenetic inference that MSI1 is part of the Rpd3L complex. Reason: The node (PTN001110151) groups the yeast RbAp48-like WD40 paralogs (Msi1, Hat2, Ume1, Wtm1, Wtm2) with S. pombe Prw1; the Rpd3L assertion rests on Ume1 (and Prw1 for the Clr6 complex). In S. cerevisiae the WD40 subunit of Rpd3L is Ume1, which is shared between Rpd3L and Rpd3S, and the GO definitions of both GO:0033698 and GO:0070210 name Ume1p, not Msi1p, among the budding-yeast subunits. Msi1 has been purified as the small subunit of CAF-1 and has a separate CAF-1-independent cytoplasmic role; it is not reported in Rpd3L purifications. The complex membership is a paralog-specific property (Ume1) that does not transfer to Msi1. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001110151 · PTN001110151 SUPPORTS SOURCE BUT NOT TARGET Node spans the yeast RbAp48-like WD40 paralogs; Rpd3L membership is a property of the Ume1 (and S. pombe Prw1) lineage, and budding-yeast Rpd3L definitions name Ume1p, not Msi1p. SGD:S000006060 · UME1 SUPPORTS SOURCE BUT NOT TARGET Ume1 is the WD40 subunit shared by Rpd3L and Rpd3S; its complex membership does not transfer to the CAF-1 subunit Msi1. Supporting Evidence: PMID:16286008 The smaller complex, Rpd3C(S), shares Sin3 and Ume1 with Rpd3C(L) but contains the unique subunits Rco1 and Eaf3. PMID:9030687 The gene encoding the p50 subunit of yeast CAF-I (CAC3) is similar to the human p48 CAF-I subunit and was identified previously as MSI1
GO:0042393 histone binding	IDA PMID:16503640 Chromatin assembly factor 1 interacts with histone H3 methyl...	KEEP AS NON CORE	Summary: MSI1 as a contributor to histone binding by CAF-1, based on co-purification of CAF-1 with histones H3 and H4 from yeast cells. Reason: The contributes_to qualifier correctly frames this as an activity of the complex. However, recombinant yeast Cac3 binds H3-H4 weakly or not detectably on its own (reports differ) and is not required for robust histone binding by CAF-1; the histone-binding site is formed by the Cac1 acidic region together with Cac2. MSI1's contribution to histone binding is therefore at most accessory. Retained as non-core because the complex-level statement is true, but it should not be taken as evidence that Msi1 is a histone-binding module in yeast CAF-1 (unlike the metazoan RbAp48/p55 orthologs). Supporting Evidence: PMID:16503640 we have purified a complex containing CAF-1 and H3 and H4 from yeast cells PMID:30239791 In fact, the yeast Cac3 exhibits no interaction with H3–H4, even at micromolar concentrations in vitro (63), and Cac3 is not required for robust histone binding in the context of CAF-1 (62). PMID:28315523 On CAF-1, the H3-H4 binding site is formed by the acidic region of Cac1 (Liu et al., 2016), in conjunction with Cac1-bound Cac2 (Mattiroli et al., 2017). file:yeast/MSI1/MSI1-deep-research-falcon.md Cac3 contributes to complex organization and affinity but is not the principal productive H3–H4-binding/deposition module
GO:0070210 Rpd3L-Expanded complex	IBA GO_REF:0000033	REMOVE	Summary: Phylogenetic inference that MSI1 is part of the Rpd3L-Expanded complex. Reason: The node (PTN001110151) groups the yeast RbAp48-like WD40 paralogs (Msi1, Hat2, Ume1, Wtm1, Wtm2) with S. pombe Prw1; the Rpd3L assertion rests on Ume1 (and Prw1 for the Clr6 complex). In S. cerevisiae the WD40 subunit of Rpd3L is Ume1, which is shared between Rpd3L and Rpd3S, and the GO definitions of both GO:0033698 and GO:0070210 name Ume1p, not Msi1p, among the budding-yeast subunits. Msi1 has been purified as the small subunit of CAF-1 and has a separate CAF-1-independent cytoplasmic role; it is not reported in Rpd3L purifications. The complex membership is a paralog-specific property (Ume1) that does not transfer to Msi1. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001110151 · PTN001110151 SUPPORTS SOURCE BUT NOT TARGET Node spans the yeast RbAp48-like WD40 paralogs; Rpd3L membership is a property of the Ume1 (and S. pombe Prw1) lineage, and budding-yeast Rpd3L definitions name Ume1p, not Msi1p. SGD:S000006060 · UME1 SUPPORTS SOURCE BUT NOT TARGET Ume1 is the WD40 subunit shared by Rpd3L and Rpd3S; its complex membership does not transfer to the CAF-1 subunit Msi1. Supporting Evidence: PMID:16286008 The smaller complex, Rpd3C(S), shares Sin3 and Ume1 with Rpd3C(L) but contains the unique subunits Rco1 and Eaf3. PMID:9030687 The gene encoding the p50 subunit of yeast CAF-I (CAC3) is similar to the human p48 CAF-I subunit and was identified previously as MSI1

Gene Description

Existing Annotations Review

Core Functions

Msi1/Cac3 is the WD40 small subunit of CAF-1, binding the Cac1 scaffold and supporting (but not forming) the H3-H4 binding interface; as part of CAF-1 it is required in vivo for replication-coupled chromatin assembly functions such as telomeric silencing.

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