RLF2 (CAC1) encodes Cac1, the large (p150-like) scaffold subunit of chromatin assembly factor 1 (CAF-1), the heterotrimeric H3-H4 histone chaperone (Cac1-Cac2-Cac3/Msi1) that deposits newly synthesized histones H3-H4 onto DNA immediately behind the replication fork and at sites of repair synthesis. Cac1 organizes the complex, binding Cac2 and Cac3 through separate regions; its acidic region forms the histone-binding surface together with Cac2; a PIP box recruits CAF-1 to PCNA; and two DNA-binding modules (the KER coiled-coil region and a C-terminal winged helix domain) engage DNA once H3-H4 is bound, allowing two CAF-1-H3-H4 complexes to assemble an (H3-H4)2 tetrasome. Cac1 acts in the nucleus on replicating chromatin, and its association with chromatin is regulated by Cdc28 and Cdc7 phosphorylation in S phase. CAF-1 is not essential for growth, but cac1 mutants have reduced telomeric and HM-locus silencing (originally identified as altered Rap1 localization, hence RLF2), sensitivity to UV and double-strand-break agents, and centromeric chromatin defects in combination with hir mutations.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000510 H3-H4 histone complex chaperone activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that RLF2/Cac1 has H3-H4 histone complex chaperone activity. Reason: Cac1 is the scaffold subunit of CAF-1 and carries the acidic (ED) histone-binding region and the winged-helix domain; a fragment of Cac1 alone can assemble tetrasomes, albeit less efficiently than Cac1-Cac2. The CAF-1 trimer binds one H3-H4 dimer and two CAF-1-H3-H4 complexes deposit an (H3-H4)2 tetramer onto DNA, which is the defining activity of an H3-H4 histone complex chaperone. Supporting Evidence: PMID:28315523 Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that associates with the replisome and orchestrates chromatin assembly following DNA synthesis. PMID:30239791 The CAF-1 trimer binds to a single H3-H4 dimer, which induces a conformational rearrangement in CAF-1 promoting its interaction with substrate DNA. PMID:28315525 our data are in agreement with the model that Cac1 contributes substantially to H3-H4 binding while Cac2 and Cac3 provide accessory interactions file:yeast/RLF2/RLF2-deep-research-falcon.md It is a nuclear histone-chaperone scaffold. |
| GO:0000775 chromosome, centromeric region | IDA PMID:11782447 Chromatin assembly factor I and Hir proteins contribute to b... | KEEP AS NON CORE | Summary: RLF2/CAF-I is enriched at centromeres (ChIP). Reason: Sharp et al. report that CAF-I subunits are enriched at centromeres and, redundantly with Hir proteins, contribute to functional kinetochore chromatin. The localization is credible (abstract states it directly; full text not cached) but reflects one of several genomic sites where CAF-1 assembles chromatin rather than a dedicated centromeric role. Supporting Evidence: PMID:11782447 CAF-I subunits and Hir1 are enriched at centromeres, indicating that these proteins make a direct contribution to centromeric chromatin structures |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that RLF2/Cac1 is active on chromatin. Reason: Cac1 associates with chromatin in S phase, regulated by CDK phosphorylation and PCNA binding. Supporting Evidence: PMID:25602519 The association of CAF-I with chromatin is impaired in a cdc28-1 mutant PMID:11089978 All silencing defective mutants showed reduced binding to CAF-1 in vitro and altered chromatin association of the CAF-1 large subunit in vivo. |
| GO:0000785 chromatin | IDA PMID:25602519 CDC28 phosphorylates Cac1p and regulates the association of ... | ACCEPT | Summary: Cac1p associates with chromatin in early S phase (chromatin fractionation). Reason: Jeffery et al. show CAF-I association with chromatin that depends on Cdc28 phosphorylation of Cac1p; Zhang et al. independently show PCNA-dependent chromatin association of the CAF-1 large subunit. Chromatin is where CAF-1 acts. Supporting Evidence: PMID:25602519 The association of CAF-I with chromatin is impaired in a cdc28-1 mutant PMID:11089978 All silencing defective mutants showed reduced binding to CAF-1 in vitro and altered chromatin association of the CAF-1 large subunit in vivo. |
| GO:0000786 nucleosome | IDA PMID:30239791 Mechanistic insights into histone deposition and nucleosome ... | REMOVE | Summary: Complex Portal annotation placing RLF2 (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-1β’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 RLF2 and Msi1/Cac3. 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:11731480 The silencing complex SAS-I links histone acetylation to the... | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and Sas2. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. The Cac1-Sas2 link to the SAS-I acetyltransferase is of interest for silencing but does not define a Cac1 molecular function. |
| GO:0005515 protein binding | IPI PMID:11731480 The silencing complex SAS-I links histone acetylation to the... | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and Sas4. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. The Cac1-SAS-I association does not define a Cac1 molecular function. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and Msi1/Cac3. 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 RLF2 and Msi1/Cac3. 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:17825065 Yeast two-hybrid analysis of the origin recognition complex ... | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and Orc3. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. Two-hybrid and interactome detections of an ORC association are not linked to a defined Cac1 activity. |
| GO:0005515 protein binding | IPI PMID:20967232 Subtle alterations in PCNA-partner interactions severely imp... | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and PCNA (Pol30). Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. The Cac1-PCNA interaction (via the Cac1 PIP box) is biologically important for recruiting CAF-1 to replication forks and repair sites, but GO has no specific PCNA- or sliding-clamp-binding molecular function term; the consequence is captured by DNA replication-dependent chromatin assembly (GO:0006335). |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and Msi1/Cac3. 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 RLF2 and PCNA (Pol30). Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. The Cac1-PCNA interaction (via the Cac1 PIP box) is biologically important for recruiting CAF-1 to replication forks and repair sites, but GO has no specific PCNA- or sliding-clamp-binding molecular function term; the consequence is captured by DNA replication-dependent chromatin assembly (GO:0006335). |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and Orc3. Reason: GO:0005515 protein binding is uninformative about molecular function. Removal does not mean the reported interaction is false. Two-hybrid and interactome detections of an ORC association are not linked to a defined Cac1 activity. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Generic protein binding (IPI) between RLF2 and Msi1/Cac3. 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 RLF2 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:9030688 RLF2, a subunit of yeast chromatin assembly factor-I, is req... | ACCEPT | Summary: Epitope-tagged Rlf2p localizes to the nucleus (immunofluorescence). Reason: Direct localization consistent with CAF-1 function on nuclear chromatin. Supporting Evidence: PMID:9030688 epitope-tagged Rlf2p expressed from the GAL10 promoter localizes to the nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping places RLF2 in the nucleus. Reason: Consistent with direct localization evidence and with CAF-1 function on nuclear chromatin. |
| GO:0006260 DNA replication | NAS PMID:30239791 Mechanistic insights into histone deposition and nucleosome ... | MARK AS OVER ANNOTATED | Summary: Complex Portal NAS annotation of RLF2/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 RLF2/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 RLF2/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:0006334 nucleosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that RLF2/Cac1 is involved in nucleosome assembly. Reason: Correct: CAF-1 performs the first step of nucleosome assembly, deposition of (H3-H4)2 tetramers. The more specific GO:0006335 is also annotated; this parent term is accurate and harmless. Supporting Evidence: PMID:30239791 Two CAF-1β’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 | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that RLF2/Cac1 is involved in DNA replication-dependent chromatin assembly. Reason: Core, conserved function of CAF-1; agrees with direct yeast biochemical and genetic evidence. 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 RLF2/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-1β’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: RLF2 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:0006335 DNA replication-dependent chromatin assembly | IMP PMID:9030688 RLF2, a subunit of yeast chromatin assembly factor-I, is req... | ACCEPT | Summary: rlf2 mutants perturb telomeric chromatin; RLF2 is identical to CAC1. Reason: Enomoto et al. show rlf2 mutants have reduced telomeric silencing and altered Rap1p distribution, identify RLF2 as CAC1, and propose that Rlf2p facilitates assembly of histones into chromatin. Together with the biochemical assays of Kaufman et al., this supports the in vivo role in replication-coupled chromatin assembly. Supporting Evidence: PMID:9030688 We propose that Rlf2p facilitates the efficient and timely assembly of histones into telomeric chromatin PMID:9030688 This study provides evidence that yCAF-I is required for the function and organization of telomeric chromatin in vivo |
| GO:0033186 CAF-1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that RLF2 is a CAF-1 complex subunit. Reason: The IBA agrees with direct biochemical evidence for the yeast protein (it appears among the IBA sources, as expected when the target carries its own experimental annotation). CAF-1 subunit composition is conserved from yeast to human. Supporting Evidence: PMID:9030687 The CAC1 and CAC2 (chromatin assembly complex) genes encode proteins similar to the p150 and p60 subunits of human CAF-I, respectively |
| GO:0033186 CAF-1 complex | IDA PMID:9030687 Ultraviolet radiation sensitivity and reduction of telomeric... | ACCEPT | Summary: RLF2 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 RLF2 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:0042393 histone binding | IDA PMID:16503640 Chromatin assembly factor 1 interacts with histone H3 methyl... | ACCEPT | Summary: RLF2 contributes to H3-H4 binding by CAF-1; CAF-1 was co-purified with H3 and H4 from yeast cells. Reason: Yeast CAF-1 was isolated from cells in complex with H3 and H4 carrying newly-synthesized histone marks (H4K5/K12ac, H3K56ac). Structural work shows the H3-H4 binding site is formed by the acidic region of Cac1 in conjunction with Cac2, so contributes_to histone binding is appropriate for RLF2. The more specific activity, H3-H4 histone complex chaperone activity, is captured in core_functions. Supporting Evidence: PMID:16503640 we have purified a complex containing CAF-1 and H3 and H4 from yeast cells 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). |
| GO:0003677 DNA binding | IDA PMID:26908650 A DNA binding winged helix domain in CAF-1 functions with PC... | NEW | Summary: Proposed: Cac1 binds DNA directly through its C-terminal winged helix domain and its KER region. Reason: Zhang et al. solved the Cac1 C-terminal winged-helix domain and showed it binds DNA sequence-independently; mutations abolishing DNA binding cause silencing defects and damage sensitivity. Sauer et al. identified a second DNA-binding region (KER) in Cac1 required for high-affinity DNA binding by the trimer, and Mattiroli et al. showed H3-H4 binding activates WHD-DNA engagement during tetrasome assembly. DNA binding is a direct, mechanistically required activity of Cac1 not captured by any existing row. Supporting Evidence: PMID:26908650 We show that Cac1C forms a winged helix domain (WHD) and binds DNA in a sequence-independent manner. PMID:26908650 Mutations in Cac1C that abolish DNA binding result in defects in transcriptional silencing and increased sensitivity to DNA damaging agents PMID:28315525 We identify a new DNA-binding domain in the large Cac1 subunit of CAF1, which is required for high-affinity DNA binding by the CAF1 three-subunit complex PMID:28315523 We show that yeast CAF-1 binding to a H3-H4 dimer activates the Cac1 winged helix domain interaction with DNA. |
| GO:0031509 subtelomeric heterochromatin formation | IMP PMID:9030687 Ultraviolet radiation sensitivity and reduction of telomeric... | NEW | Summary: Proposed: RLF2, as a CAF-1 subunit, is involved in subtelomeric heterochromatin formation. Reason: Deletion of any CAC gene strongly reduces silencing of telomere-adjacent reporters, and loss of CAF-I subunits destabilizes HML repression. Participation test: CAF-1 performs a step of the process itself, depositing H3-H4 into the chromatin that Sir proteins then compact (Enomoto et al. propose Rlf2p facilitates timely assembly of histones into telomeric chromatin); it is not merely a substrate or upstream requirement. Comparator check: the partner H3-H4 chaperone ASF1 (P32447) already carries GO:0031509 and GO:0030466 by IGI (PMID:15840725), as does SIR3 by IMP, so the term is used for chromatin-assembly factors in yeast; the CAF-1 subunits currently carry no heterochromatin-formation annotation at all in GOA. This is proposed as non-core relative to the general replication-coupled assembly function. Supporting Evidence: PMID:9030687 Deletion of CAC genes also strongly reduces silencing of genes adjacent to telomeric DNA PMID:9030688 We propose that Rlf2p facilitates the efficient and timely assembly of histones into telomeric chromatin PMID:26908650 Mutations in Cac1C that abolish DNA binding result in defects in transcriptional silencing and increased sensitivity to DNA damaging agents |
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Download this section (compressed HTML)Q: Does the PCNA-binding PIP box of Cac1 warrant a dedicated GO molecular function term (sliding clamp binding), given its central role in recruiting CAF-1 to replication and repair sites?
Q: Should CAF-1 subunits carry silent mating-type cassette heterochromatin formation (GO:0030466), given that CAF-I is needed for maintenance but not re-establishment of HML silencing?
Q: How do Cdc28 and Cdc7 phosphorylation of Cac1 coordinate CAF-1 chromatin loading with S-phase progression independently of PCNA binding?
Experiment: Combine Cac1 WHD and KER DNA-binding mutants with PIP-box mutants and measure CAF-1 occupancy on nascent chromatin (e.g. by nascent-chromatin capture) and tetrasome assembly kinetics in vivo.
Hypothesis: DNA binding and PCNA binding act additively to retain CAF-1 behind the fork, and loss of both abolishes replication-coupled H3-H4 deposition.
Type: genetic and genomic
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