| 1996 |
Yeast SUB1 was isolated as a suppressor of TFIIB mutations (E62G, R78H); SUB1 binds directly to TFIIB in vitro and specifically inhibits the formation of TBP-TFIIB-promoter complexes, suggesting a role in TFIIB release during transcription initiation. |
Genetic suppressor screen, in vitro binding assay (pulldown), in vivo transcriptional activation assay |
The EMBO journal |
High |
8617240
|
| 1999 |
Allele-specific genetic interactions between ssu72 and sub1 with TFIIB (sua7) mutants demonstrate functional interactions among TFIIB, Ssu72, and Sub1 that influence the accuracy of transcription start site selection by RNA polymerase II. |
Error-prone PCR mutagenesis of TFIIB, genetic interaction analysis (synthetic lethality/suppression), allele-specificity tests |
Genetics |
Medium |
10511545
|
| 2003 |
Sub1 physically interacts with the Pta1 subunit of CPF (cleavage/polyadenylation factor), and overexpression of SUB1 suppresses growth and processing defects of a pta1 mutation; physical interactions of Ssu72 and Sub1 with Pta1 are mutually exclusive, linking transcription initiation and 3' end processing machineries. |
Biochemical co-purification, genetic suppression (overexpression of SUB1 rescuing pta1 mutant), in vitro cleavage assay |
Genes & development |
High |
12704082
|
| 2005 |
Sub1 and Rna15 (yeast CstF-64 homolog) are recruited to promoters and present along the length of several yeast genes; deletion of SUB1 causes decreased accumulation of Fcp1, altered RNAP II CTD phosphorylation, and decreased crosslinking of RNAP II to transcribed genes, indicating Sub1 facilitates elongation by influencing CTD-modifying enzymes. |
Chromatin immunoprecipitation (ChIP), allele-specific genetic interactions with KIN28 and FCP1, Western blot |
The EMBO journal |
High |
15692559
|
| 2008 |
Sub1 functions as a transcriptional repressor at the IMD2 gene in yeast: deletion of SUB1 increases IMD2 expression, and Sub1 localizes to the IMD2 promoter region; the upstream region of the transcription start site is required for Sub1-mediated repression. |
ChIP, gene expression analysis (RT-PCR/Northern), genetic interaction with dst1 (TFIIS) |
Genes to cells : devoted to molecular & cellular mechanisms |
Medium |
18823333
|
| 2009 |
Sub1 is present at the promoter of every constitutively transcribed RNAP II and RNAP III gene tested (but not RNAP I), and deletion of SUB1 reduces promoter-associated RNAP II or III levels without reducing TBP levels, indicating Sub1 facilitates polymerase recruitment at both RNAP II and RNAP III genes. |
ChIP, synthetic genetic array screen (SGA), genetic interactions with HOG pathway genes |
Molecular and cellular biology |
High |
19204085
|
| 2009 |
Sub1 is present on Pol III-transcribed genes genome-wide, interacts with components of the Pol III transcription system, and stimulates the initiation and reinitiation steps in a system reconstituted with all recombinant factors; Sub1 is required for optimal Pol III gene transcription in exponentially growing cells. |
Genome-wide ChIP-chip, in vitro reconstituted transcription assay with recombinant factors, genetic analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19706510
|
| 2010 |
Sub1 globally regulates RNA polymerase II CTD phosphorylation: SUB1 deletion increased CTD phosphorylation by Kin28, Bur1, and Ctk1 but decreased it by Srb10; ChIP showed SUB1 deletion decreased Srb10 chromatin association but increased Kin28 and Ctk1 chromatin association on active genes. |
In vitro kinase assays, ChIP, genetic interactions with all four CTD kinase genes |
Molecular and cellular biology |
High |
20823273
|
| 2011 |
Sub1 (homolog of mammalian coactivator PC4) is a component of RNA polymerase II preinitiation complexes (PICs); Sub1 localizes near the transcription bubble in vitro and binds to promoters in vivo dependent upon PIC assembly; Sub1 and RPA compete for a common ssDNA binding site (nontemplate strand), with RPA increasing at active promoters when Sub1 is deleted or its ssDNA-binding is mutated. |
Quantitative proteomic analysis of RNApII PICs (mass spectrometry), in vitro transcription bubble binding, ChIP, genetic interactions |
Molecular cell |
High |
22055186
|
| 2012 |
Sub1 genetically interacts with the elongation factor Spt5 gene; Sub1 influences Spt5 phosphorylation of the RNAPII CTD by kinase Bur1; Sub1 and Spt5 co-purify in the same complex during early transcription elongation; Sub1 influences Spt5-Rpb1 interaction and transcription elongation rate of constitutive and inducible genes. |
Genetic interaction analysis, co-purification (complex isolation), ChIP, in vitro kinase assay |
Molecular biology of the cell |
High |
22973055
|
| 2013 |
SUB1 is required for NHEJ repair of DSBs in plasmid DNA but NOT in chromosomal DNA in yeast, demonstrating a differential requirement for Sub1 in these two NHEJ pathways. |
NHEJ assay (plasmid re-circularization and chromosomal HO/I-SceI break repair), deletion mutant analysis |
PloS one |
Medium |
23554872
|
| 2014 |
Sub1 and Maf1 exert opposite effects on RNA polymerase III transcription and on yeast chronological lifespan; cells lacking Sub1 show a delay in re-proliferation and transcriptional reactivation after quiescence, and Sub1 loss causes premature death dependent on Ras/PKA and Tor1/Sch9 signalling pathways. |
Chronological lifespan assay, gene expression analysis, genetic interactions with signaling pathway mutants |
PloS one |
Medium |
25531541
|
| 2015 |
Yeast Sub1 and human PC4 preferentially bind to G-quadruplex (G4) DNA over other DNA structures, as identified by G-quadruplex bait pulldown and quantitative LC-MS/MS proteomics, and confirmed by ChIP showing in vivo G4 binding. |
G-quadruplex bait pulldown, quantitative LC-MS/MS, ChIP |
Chemical communications (Cambridge, England) |
Medium |
25813861
|
| 2015 |
Sub1 protects DNA from oxidative damage in vivo and in vitro: SUB1 mRNA is induced by oxidative stress, sub1Δ mutants show increased chromosomal DNA strand breaks after peroxide treatment, and purified Sub1 protein directly protects DNA from oxidative damage in a metal ion catalyzed oxidation assay. |
In vitro DNA protection assay (metal ion catalyzed oxidation), in vivo comet assay/strand break analysis, RT-PCR for stress induction |
Molecular and cellular biochemistry |
Medium |
26708217
|
| 2016 |
SUB1 knockdown in prostate cancer cells results in reduced cell proliferation, invasion, and migration in vitro and tumor growth/metastasis in vivo; ChIP revealed that SUB1 binds to the promoter regions of oncogenes PLK1, C-MYC, and BUB1B and regulates their expression; SUB1 downregulates CDKN1B expression. |
siRNA knockdown, in vitro invasion/migration assays, in vivo xenograft model, ChIP, gene expression analysis |
Oncogene |
Medium |
27270442
|
| 2016 |
Sub1 binds to promoters of approximately half the yeast genome (by ChIP-Seq); sub1Δ mutant RNA-Seq shows the majority of genes have no change in expression, but of those that do change, most show decreased expression, consistent with Sub1 acting as a positive transcriptional regulator; Sub1 deletion increases basal expression of pheromone-inducible genes including FUS1 and IMD2. |
ChIP-Seq (first reported for Sub1), RNA-Seq of sub1Δ mutant, FACS-based barcode sequencing screen |
G3 (Bethesda, Md.) |
Medium |
26837954
|
| 2017 |
Sub1 physically interacts with the RNAPII stalk domain (Rpb4/7 heterodimer), likely through its C-terminal region, and associates with the phosphatase Fcp1; a complete CTD is necessary for Sub1 association with chromatin and RNAPII; Sub1-Rpb4/7-Fcp1 interaction modulates CTD phosphorylation; Sub1 interaction with Rpb4/7 also influences transcription start site selection and elongation rate via the clamp domain. |
Co-immunoprecipitation (Co-IP), ChIP, genetic interaction analysis (clamp domain mutants), yeast two-hybrid |
Nucleic acids research |
High |
27924005
|
| 2017 |
Sub1 disruption in yeast leads to genome-wide redistribution of APOBEC-induced clustered mutations; inactivation of Sub1 strongly reduces deaminase-induced mutation frequency at CAN1 but does not decrease total SNV load; mutations redistribute toward transcription initiation regions, implicating Sub1 in protection of ssDNA during transcription from deaminase activity. |
Whole-genome sequencing of drug-resistant mutants, genetic deletion of SUB1, mutation frequency assay |
PLoS genetics |
Medium |
25941824
|
| 2017 |
Sub1 and its human homolog PC4 suppress G4 DNA-associated genome instability at co-transcriptionally formed G4 structures; Sub1 interacts specifically with co-transcriptionally formed G4 DNA in vivo; Sub1 physically and genetically interacts with the G4-resolving helicase Pif1, suggesting a cooperative mechanism in G4 suppression. |
Reporter assay for G4-induced recombination in yeast, ChIP, genetic interaction analysis, G4 ligand sensitivity assay |
Nucleic acids research |
Medium |
28369605
|
| 2015 |
Deletion of SUB1 significantly increased sporulation efficiency in yeast; SUB1 transcript and protein levels are downregulated during sporulation; Sub1 associates with chromatin at middle sporulation gene loci in a temporal pattern inversely correlated with their expression; SUB1 genetically interacts with HOS2 (component of Set3 repressor complex), suggesting Sub1 functions with this complex to repress sporulation genes. |
Sporulation efficiency assay, RT-qPCR, Western blot, ChIP, genetic interaction (sub1Δ × hos2Δ), complementation with human PC4 |
PloS one |
Medium |
26147804
|
| 2022 |
The Role of Sub1 in transcription elongation depends on its C-terminal (CT) region and is independent of the ssDNA-binding domain (ssDBD); specific residues in the ssDBD are required for DNA interaction in vivo and Sub1 recruitment to promoters, while the CT region is required for transcription elongation by RNAPII. |
Site-directed mutagenesis, ChIP, genetic analysis, in vivo transcription assays |
Cells |
Medium |
36291192
|
| 2018 |
Crystal structure of MoSub1 (Sub1/PC4 ortholog from rice blast fungus) complexed with ssDNA reveals that a phosphate ion at the protein-DNA interface bridges Lys84 of the protein and two nucleotides, altering the DNA binding mode (L mode vs. straight mode), providing structural insight into how phosphorylation modulates Sub1 ssDNA binding. |
X-ray crystallography (2.04 Å resolution), SAXS analysis |
Proteins |
High |
30561148
|
| 2021 |
In macrophages, SUB1 mediates pro-atherogenic TLR2/TLR4 signaling effects; myeloid-specific Sub1 knockout reduces atherosclerosis in ApoE-/- mice; SUB1 activates Irf1 transcription in a casein kinase 2 (Ck2)-dependent manner; Sub1-knockout macrophages show decreased Irf1 expression and enhanced M2 polarization; artificial Irf1 overexpression in Sub1-knockout macrophages restores M1 skewing. |
Myeloid-specific conditional knockout in ApoE-/- mice, bone marrow transplantation, promoter analysis, Irf1 overexpression rescue experiment, macrophage polarization assays |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
High |
34378353
|
| 2024 |
SUB1 (human PC4) directly binds to N2-alkyl-dG DNA lesions and promotes their repair in human cells; SUB1 binds preferentially to both cis and trans diastereomers of N2-BPDE-dG over unmodified dG; genetic ablation of SUB1 confers diminished repair of both N2-BPDE-dG diastereomers; SUB1 depletion sensitizes cells to BPDE. |
Photo-crosslinking coupled with quantitative mass spectrometry proteomics, in vitro DNA binding assays, cell-based repair assays with SUB1 knockout |
Journal of the American Chemical Society |
High |
39101269
|
| 2024 |
SUB1 promotes colorectal cancer metastasis by activating NF-κB signaling: SUB1 interacts with and increases the protein level of E3 ubiquitin ligase UBR5, which mediates Lys11-linked polyubiquitination and degradation of NF-κB negative regulator UBXN1, thereby activating NF-κB and its transcriptional targets CXCL1 and CXCL3. |
Co-immunoprecipitation, ubiquitination assay (Lys11 linkage-specific), siRNA knockdown, in vivo xenograft metastasis model, gene expression analysis |
Science China. Life sciences |
High |
38240906
|
| 2025 |
SUB1 expression is induced by the TCR-IRF4 transcription factor axis in CD4+ T cells; SUB1 undergoes liquid-liquid phase separation to form condensates that open chromatin at Junb and Dock2 loci; SUB1 directly trans-activates Junb transcription and partners with JUNB to amplify Dock2 transcription; conditional T cell-specific Sub1 deletion reduces DOCK2 expression, inhibits Rac-dependent actin polymerization and T cell motility, and prevents onset of experimental autoimmune encephalomyelitis. |
Conditional T cell-specific knockout mouse model, ATAC-seq, ChIP, phase separation assay, T cell motility assay, EAE induction model |
Immunity |
High |
41371223
|
| 2025 |
SUB1 depletion increases replication stress at ALT telomeres, profoundly impairing ALT cancer cell growth without impacting telomerase-positive cells; during replication stress, SUB1 is recruited to stalled forks and ALT telomeres via its ssDNA-binding domain; RPA depletion potentiates SUB1 recruitment, suggesting competition for ssDNA; SUB1 depletion combined with FANCM depletion or RS-inducing drugs triggers replication catastrophe in ALT cells. |
CRISPR fitness screens, siRNA knockdown, replication stress assays, immunofluorescence/localization at stalled forks, genetic epistasis with FANCM and RPA |
Proceedings of the National Academy of Sciences of the United States of America |
High |
39772744
|
| 2016 |
Osmostress transcription factor Hot1 physically associates with Sub1 and recruits it (along with elongation complex Spt4/5) to the promoter/5'-coding region of osmostress genes under hyperosmotic stress conditions. |
Co-immunoprecipitation (physical interaction), ChIP, genetic interaction analysis |
The Biochemical journal |
Medium |
27480106
|
| 2023 |
Pif1 helicase physically interacts with Sub1 and catalyzes ATP-dependent disruption of Sub1-bound G4 DNA structures, remodeling Sub1-G4 protein-nucleic acid complexes. |
In vitro helicase/displacement assay, protein-protein interaction assay, ATPase-dependent mechanism analysis |
Biochemistry |
Medium |
37948114
|