Affinage

Showing SEM1 — DSS1 is a alias.

SEM1

Putative protein SEM1, isoform 2 · UniProt Q6ZVN7

Length
128 aa
Mass
14.1 kDa
Annotated
2026-06-10
58 papers in source corpus 34 papers cited in narrative 36 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SEM1/DSS1 is a small intrinsically disordered protein that functions as a modular cofactor across multiple macromolecular machines, using short conserved acidic and hydrophobic segments to grasp distinct partners (PMID:25306921, PMID:24412063). In the 26S proteasome it is a stoichiometric lid subunit that tethers the Rpn3 and Rpn7 subunits through two acidic segments separated by a flexible linker, acting as a molecular glue/chaperone during lid biogenesis and stabilizing the regulatory particle; its loss causes accumulation of polyubiquitinated proteins and synthetic defects with other proteasome subunits (PMID:15572408, PMID:24412063, PMID:23643786). Within this context it also serves directly as a proteasomal ubiquitin receptor, binding K48- and K63-linked chains via complementary acidic and hydrophobic surfaces (PMID:25306921, PMID:18775730). In a separate role, SEM1/DSS1 is an obligate partner of BRCA2 (and the fungal ortholog Brh2) in homologous recombination: it binds the C-terminal OB-fold/DNA-binding region (PMID:12228710, PMID:10373512), is required for BRCA2 protein stability and for DNA-damage-induced RAD51 focus formation (PMID:16205630, PMID:15359272, PMID:14580353), and allosterically restrains BRCA2/Brh2 dsDNA binding to enforce ssDNA targeting of RAD51 — a function in which the DSS1 C-terminal helix (residue R57) is critical and whose disruption decreases HR efficiency, destabilizes stalled forks, and causes R-loop accumulation (PMID:19919104, PMID:39152168). DSS1 additionally acts as a DNA mimic that attenuates RPA affinity for ssDNA to promote RPA-to-RAD51 exchange (PMID:26145171) and counteracts BRCA2 self-oligomerization (PMID:32609828). Beyond the proteasome and HR, SEM1/DSS1 is a functional component of the TREX-2 (Sac3-Thp1) complex at the nuclear pore required for mRNA export and transcription-coupled genome stability (PMID:19289793, PMID:19061648), a subunit of the Thp3-Csn12-Sem1 splicing complex where it stabilizes Csn12 (PMID:35904806), and an integral subunit of the Integrator-PP2A (INTAC) complex, where tryptophan 39 mediates the INTAC interaction to regulate paused RNA Pol II (PMID:40617815). The dispensability of the BRCA2-DSS1 interaction for meiotic RAD51 loading establishes context-specific requirements for its HR function (PMID:35365640).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Established the two foundational partnerships that frame DSS1 biology — physical association with BRCA2 and a genetic link to exocytosis/differentiation — first placing the protein within DNA repair and secretory contexts.

    Evidence Yeast/mammalian two-hybrid and endogenous co-IP for BRCA2 binding; multicopy suppressor and co-sedimentation in S. cerevisiae for exocyst interaction with cross-species mouse rescue

    PMID:10373512 PMID:9927667

    Open questions at the time
    • BRCA2-binding region defined to residues 2472-2957 but no atomic detail at this stage
    • exocyst/pseudohyphal role not mechanistically connected to other functions
  2. 2002 High

    Provided the structural basis for the BRCA2-DSS1 interaction and linked it to ssDNA binding and RAD51-mediated recombination, defining DSS1 as part of the DNA-binding machinery of BRCA2.

    Evidence X-ray crystallography of the BRCA2 DNA-binding domain bound to DSS1 with in vitro DNA binding and RAD51 recombination assays

    PMID:12228710

    Open questions at the time
    • functional role of DSS1 in the complex not resolved structurally
    • did not establish whether DSS1 stabilizes BRCA2 or directly regulates DNA binding
  3. 2003 High

    Demonstrated genetically that DSS1 is an essential component of the BRCA2/Brh2-dependent recombinational repair pathway, with loss phenocopying Brh2/Rad51 mutants.

    Evidence Gene deletion in U. maydis with radiation sensitivity, recombination, meiosis, and genome instability readouts

    PMID:14580353

    Open questions at the time
    • molecular step at which DSS1 acts not defined
    • relationship to proteasome function not addressed
  4. 2004 Medium

    Separated DSS1's recombination function from protein-stability effects, showing it is needed for RAD51 focus formation and DNA-damage targeting without affecting BRCA2/RAD51 stability or their interaction.

    Evidence RNAi knockdown with RAD51 immunofluorescence and genomic instability assays in mammalian cells; parallel genetic and imaging work in U. maydis

    PMID:15359272 PMID:15767662

    Open questions at the time
    • mechanism of how DSS1 promotes localization not resolved
    • single-lab cellular phenotype
  5. 2004 High

    Identified the conserved proteasomal role of Sem1 as a lid subcomplex component required for 26S proteasome stability, defining a second major function distinct from HR.

    Evidence Genetic suppressor screen, co-purification, polyubiquitin accumulation and synthetic lethality analysis in S. cerevisiae

    PMID:15572408

    Open questions at the time
    • precise structural placement within the lid unknown
    • whether the same molecule serves HR and proteasome roles simultaneously unresolved
  6. 2006 High

    Showed DSS1 is required for BRCA2 protein stability in human cells, providing one mechanistic basis for its HR requirement and linking it to proteasomal degradation control.

    Evidence RNAi knockdown with Western blotting and co-IP in human cell lines; parallel demonstration of conserved proteasome association in S. pombe

    PMID:16149916 PMID:16205630

    Open questions at the time
    • does not reconcile with model-organism findings where DSS1 is dispensable for Brh2 stability
    • degradation pathway for BRCA2 in DSS1 absence not fully mapped
  7. 2008 Medium

    Defined proteasome-independent roles in mRNA export and mapped the human proteasome-interaction motif, clarifying that DSS1 partitions among multiple complexes.

    Evidence E-MAP genetic interaction mapping with biochemical validation (Sac3-Thp1, Csn12 interactions); co-IP and R3IM-motif mutagenesis defining RPN3/S3 binding in human cells

    PMID:18775730 PMID:19061648

    Open questions at the time
    • how a single small protein is partitioned between complexes unknown
    • p53/gankyrin-MDM2 link from a single lab
  8. 2009 High

    Established Sem1 as a bona fide TREX-2 subunit at the nuclear pore linking mRNA export to transcription-coupled genome stability, and biochemically demonstrated allosteric regulation of Brh2 DNA binding.

    Evidence Genetic and co-purification analysis with in situ hybridization and hyper-recombination assays in yeast; in vitro DNA-binding kinetics and competition assays on Brh2-Dss1

    PMID:19289793 PMID:19919104

    Open questions at the time
    • how TREX-2 and proteasome pools are regulated unknown
    • allosteric mechanism inferred biochemically without structure
  9. 2013 Medium

    Localized Sem1 structurally as a molecular glue stabilizing the Rpn3/Rpn7 heterodimer and extended its TREX-2 role to SAGA-dependent transcription activation and H2B deubiquitylation.

    Evidence Cryo-EM with site-specific cross-linking of the proteasome; ChIP and in vitro deubiquitylation/reporter assays for SAGA

    PMID:23599000 PMID:23643786

    Open questions at the time
    • moderate cryo-EM resolution
    • mechanistic link between Sem1 and H2B deubiquitylation not fully defined
  10. 2014 High

    Resolved at atomic resolution the dual proteasomal mechanism — Sem1 as a disordered chaperone that tethers Rpn3 and Rpn7 during lid biogenesis and as a ubiquitin receptor binding K48/K63 chains.

    Evidence Biochemical reconstitution with TEV site-insertion mutagenesis (tethering) and atomic-resolution structural data with mutagenesis and in vivo ubiquitin accumulation assays (ubiquitin receptor)

    PMID:24412063 PMID:25306921

    Open questions at the time
    • how the same acidic surfaces are repurposed across complexes unknown
    • in vivo balance between chaperone and receptor activities not quantified
  11. 2015 High

    Revealed that DSS1 functions as a DNA mimic, attenuating RPA-ssDNA affinity to drive RPA-to-RAD51 exchange — a direct enzymatic contribution to HR beyond stabilization.

    Evidence Biochemical reconstitution, structural analysis, acidic-domain mutagenesis, and in vivo HR assays

    PMID:26145171

    Open questions at the time
    • interplay between DNA-mimic and BRCA2-stabilizing roles in cells unresolved
    • structural model of the DSS1-RPA-ssDNA transition incomplete
  12. 2020 Medium

    Expanded DSS1's HR regulatory repertoire to controlling BRCA2 oligomeric state and modulating RAD52, indicating it tunes multiple recombination mediators.

    Evidence Biochemical assays and electron microscopy on BRCA2 self-interactions; in vitro RAD52 interaction, single-strand annealing and strand invasion assays

    PMID:31799622 PMID:32609828

    Open questions at the time
    • cellular relevance of BRCA2 oligomerization control not demonstrated
    • RAD52 modulation from a single lab
  13. 2022 High

    Provided in vivo genetic dissection in mice showing the BRCA2-DSS1 interaction is essential for somatic HR but dispensable for meiotic RAD51 loading, establishing context-dependence of the HR function.

    Evidence BRCA2 L2431P knockin mouse disrupting DSS1 binding with RAD51 foci, HR reporter, and meiosis analysis

    PMID:35365640

    Open questions at the time
    • molecular basis for meiotic bypass not fully defined
    • does not address non-HR DSS1 functions in vivo
  14. 2024 High

    Pinpointed the DSS1 C-terminal helix (R57) as the element that restrains intrinsic BRCA2 ss/dsDNA binding to enforce ssDNA-specific RAD51 loading, linking a single residue to fork stability and R-loop suppression.

    Evidence In vitro DNA binding, site-directed mutagenesis (R57Q), HR efficiency, replication fork protection, and R-loop quantification assays

    PMID:39152168

    Open questions at the time
    • structural snapshot of the regulated HD-OB1 state not resolved
    • in vivo contribution of R-loop control versus fork protection not separated
  15. 2025 High

    Identified DSS1 as an integral INTAC subunit (via W39) regulating paused RNA Pol II and revealed a separable autophagy-EMT signaling role, broadening DSS1 into transcriptional and cancer-relevant pathways.

    Evidence Structural analysis and W39 mutagenesis with transcriptional assays for INTAC; co-IP, ubiquitination, and autophagy-flux assays for the LC3/TRIM25/TWIST1 axis in renal cell carcinoma

    PMID:40617815 PMID:40695833

    Open questions at the time
    • how DSS1 distributes between INTAC, proteasome, and HR pools not quantified
    • autophagy-EMT role from a single lab at Medium confidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single small disordered protein is partitioned and regulated among the proteasome, BRCA2-HR machinery, TREX-2, the splicing complex, INTAC, and autophagy pathways — and what determines competition between these mutually exclusive complexes — remains unresolved.
  • no quantitative cellular partitioning of DSS1 across complexes
  • regulatory inputs (PTMs, expression) controlling complex choice largely uncharacterized
  • human relevance of fishhook/CK2-phosphorylation regulation seen only in fission yeast

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2 GO:0044183 protein folding chaperone 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-73894 DNA Repair 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-74160 Gene expression (Transcription) 2
Partners
BRCA2CSN12LC3PCID2RAD52RPARPN3/S3RPN7
Complex memberships
26S proteasome lidBRCA2-DSS1 complexIntegrator-PP2A (INTAC)TREX-2 (Sac3-Thp1/GANP-PCID2)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Crystal structure of a ~90 kDa BRCA2 domain bound to DSS1 (SEM1) at 3.1 Å resolution reveals three OB folds and a helix-turn-helix (HTH) motif; the complex binds ssDNA and the HTH motif implicates dsDNA binding; BRCA2 stimulates RAD51-mediated recombination in vitro. X-ray crystallography (3.1 Å and 3.5 Å), in vitro DNA binding assays, RAD51 recombination assay Science High 12228710
1999 DSS1 (SEM1) directly binds to the C-terminal region (amino acids 2472–2957) of BRCA2, demonstrated by yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation of transiently expressed epitope-tagged proteins, and co-IP of endogenous proteins in MCF7 cells. Yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation (endogenous and tagged) Molecular and Cellular Biology High 10373512
2015 DSS1 acts as a DNA mimic via its solvent-exposed acidic domain to attenuate RPA's affinity for ssDNA, enabling the BRCA2-DSS1 complex to physically interact with RPA and promote RPA-to-RAD51 exchange on ssDNA during homologous recombination. A mutation in the acidic domain of DSS1 compromises RPA-RAD51 exchange. Biochemical reconstitution, structural analysis, site-directed mutagenesis, in vivo HR assays Molecular Cell High 26145171
2006 RNAi knockdown of DSS1 in human cell lines leads to dramatic loss of BRCA2 protein due to increased proteasomal degradation, demonstrating that DSS1 is required for BRCA2 stability. Nearly all BRCA2 in human cells is associated with DSS1. RNAi knockdown, Western blotting, co-immunoprecipitation Oncogene High 16205630
2004 DSS1 depletion in mammalian cells impairs DNA damage-induced RAD51 focus formation and genomic stability, mirroring BRCA2 loss, but DSS1 depletion does not affect BRCA2 or RAD51 protein stability or the BRCA2-RAD51 interaction, suggesting DSS1 is required for the BRCA2-RAD51 complex to localize to DNA damage sites. RNAi knockdown, immunofluorescence (RAD51 foci), genomic instability assays EMBO Reports Medium 15359272
2004 Sem1 (DSS1 ortholog) is a component of the lid subcomplex of the 26S proteasome regulatory particle in S. cerevisiae; its loss impairs 26S proteasome stability, causes accumulation of polyubiquitinated proteins, and is synthetically lethal with proteasome subunit mutations. Rpn10 cooperates with Sem1 to maintain lid-base association. Genetic suppressor screen, co-fractionation/co-purification, polyubiquitin accumulation assay, synthetic lethality analysis Journal of Cell Science High 15572408
2014 Dss1 (Sem1) binds ubiquitin chains linked by K63 and K48 through acidic and hydrophobic residues, functioning as a 26S proteasome ubiquitin receptor. Mutations in the ubiquitin-binding site cause growth defects and accumulation of ubiquitylated proteins. Atomic resolution data show Dss1 is disordered and the complementary ubiquitin binding surface involves I13, I44, and L69. Biochemical binding assays, atomic resolution NMR/structural data, site-directed mutagenesis, in vivo ubiquitin accumulation assay Molecular Cell High 25306921
2014 Sem1 (intrinsically disordered) uses two conserved acidic segments separated by a flexible linker to simultaneously grasp proteasome subunits Rpn3 and Rpn7, functioning as a molecular tether/chaperone during proteasome lid biogenesis to enforce ordered incorporation of Rpn3 and Rpn7. TEV protease cleavage experiments show this tethering is critical for Rpn3-Sem1-Rpn7 ternary complex formation but becomes dispensable once incorporated into larger lid precursors. Biochemical reconstitution, TEV protease site-insertion mutagenesis, protein-protein interaction assays Molecular Cell High 24412063
2009 Yeast Sem1 is a functional component of the TREX-2 complex (independent of the proteasome regulatory particle) required for mRNA export and transcription elongation. Sem1 co-enriches with the NPC-associated TREX-2 complex and the COP9 signalosome. Loss of Sem1 perturbs targeting of Thp1 to the nuclear pore complex and causes transcription-associated hyper-recombination. Genetic analysis (sem1 mutants), biochemical co-purification, in situ hybridization for mRNA export, hyper-recombination assays Journal of Cell Biology High 19289793
2008 Genetic interaction mapping shows Sem1/Dss1 has a proteasome-independent role in mRNA export as a functional component of the Sac3-Thp1 complex. Sem1 also interacts with Csn12, a COP9 signalosome component. Quantitative genetic interaction mapping (E-MAP), biochemical validation Molecular Cell High 19061648
2008 Human DSS1 associates with the RPN3/S3 subunit of the 19S proteasome regulatory particle via an RPN3/S3-interacting motif (R3IM) at amino acids 15–21 of the N-terminus. The R3IM motif is required for proteasome interaction and binding to polyubiquitinated substrates. DSS1 knockdown impairs p53 degradation via the gankyrin-MDM2/HDM2 pathway. Co-immunoprecipitation, domain deletion/mutagenesis, RNAi knockdown, pull-down assays Journal of Molecular Biology Medium 18775730
2010 Partial depletion of DSS1 by RNAi in human cells reduces homologous recombinational repair (HRR) efficiency to small fractions of normal levels; residual HRR correlates with residual DSS1 expression. Proteasome inhibition only partially reproduced this effect, suggesting DSS1 has an HRR function beyond proteasomal proteolysis. RNAi knockdown, HRR reporter assay, proteasome inhibitor comparison Mutation Research Medium 20817001
2013 Cryo-EM single particle reconstruction localizes the C-terminal helix of Sem1 to the PCI domain of Rpn7 in the 26S proteasome, with the N-terminal region bridging the cleft between Rpn7 and Rpn3, confirmed by site-specific cross-linking. Sem1 can assume different conformations in different complexes, consistent with a molecular glue function stabilizing the Rpn3/Rpn7 heterodimer. Cryo-electron microscopy, site-specific cross-linking, sem1 deletion proteasome comparison Biochemical and Biophysical Research Communications Medium 23643786
2003 DSS1 ortholog in Ustilago maydis associates with the BRCA2-related protein Brh2; deletion of DSS1 causes extreme radiation sensitivity, recombination deficiency, meiotic defects, and genome instability mirroring Brh2 or Rad51 mutant phenotypes, establishing DSS1 as an essential component of the BRCA2-dependent recombinational repair pathway. Gene deletion, radiation sensitivity assay, recombination assays, meiosis analysis Molecular Cell High 14580353
2005 In U. maydis, Dss1 is not required for Brh2 stability or Brh2-Rad51 association, but is required for GFP-Rad51 focus formation after DNA damage. Brh2 variants lacking the C-terminal DNA/Dss1-binding domain but retaining the N-terminal BRC/Rad51-interacting element bypass the requirement for Dss1, revealing that the N-terminal region has an innate capacity to organize Rad51. Dss1 controls Brh2 to balance recombinational repair. Genetic suppressor screen, GFP-Rad51 live imaging, chimeric protein analysis Molecular and Cellular Biology Medium 15767662
2007 In U. maydis, Dss1 promotes dissociation of Brh2 homodimers/oligomers to monomers via interactions with the C-terminal Dss1-interacting domain, and intermolecular complementation between BRC and CRE domains of Brh2 requires Dss1, indicating Dss1 activates Brh2 by modulating its oligomeric state. Biochemical protein-protein interaction assays, intermolecular complementation genetics Molecular and Cellular Biology Medium 17261595
2009 Dss1 forms a tight complex with the C-terminal OB-fold region of Brh2 and attenuates DNA binding of full-length Brh2; dissociation of Dss1 correlates with DNA binding, and addition of excess Dss1 attenuates DNA binding without directly competing for the N-terminal DNA binding site, suggesting allosteric regulation of Brh2 DNA binding by Dss1. In vitro biochemical binding assays, DNA-binding kinetics, competition assays Biochemistry Medium 19919104
2012 Dss1 association with Brh2's C-terminal region attenuates its DNA binding potential, and the N-terminal domain of Brh2 can evict Dss1 from the C-terminal interaction surface, establishing a regulatory mechanism where Dss1 controls the sequential engagement of Brh2's N- and C-terminal domains with DNA. In vitro DNA binding assays with Brh2 fusions and truncation derivatives Biochemistry Medium 23094644
2017 In U. maydis, Dss1 modulates the CRE domain of Brh2 and its association status markedly alters the number of Rad51 protomers associating with Brh2: in complex with Dss1, only a single Rad51 protomer associates, whereas loss of Dss1 allows a large increase in Rad51 protomers bound to Brh2 concurrent with loss of Brh2 DNA binding, suggesting a feedback circuit. Biochemical protein interaction assays, stoichiometry analysis Biochemistry Medium 28616972
2020 DSS1 and ssDNA counteract BRCA2 oligomerization; DSS1 disrupts the N-to-C terminal self-interaction of BRCA2, while ssDNA modulates the N-to-N terminal self-interaction, identifying three self-interacting regions and two types of BRCA2 self-association. DSS1 thus regulates BRCA2 in an RPA-independent fashion. Biochemical assays, electron microscopy imaging Nucleic Acids Research Medium 32609828
2020 DSS1 directly interacts with RAD52, changes RAD52 oligomeric conformation, modulates its DNA binding properties, and stimulates RAD52-mediated single-strand annealing and strand invasion activities in vitro. Biochemical interaction assays, single-strand annealing assays, strand invasion assays, oligomerization analysis Nucleic Acids Research Medium 31799622
2024 DSS1 restrains the intrinsic ss/dsDNA binding activity of the BRCA2 HD-OB1 subdomains to ensure BRCA2-RAD51 targeting specifically to ssDNA. The C-terminal helix of DSS1 (including residue R57) is critical for this regulation; R57Q and other C-terminal helix mutations permit dsDNA binding of HD-OB1/BRCA2-DBD, impair BRCA2/RAD51 ssDNA loading, decrease HR efficiency, destabilize stalled replication forks, and cause R-loop accumulation. In vitro DNA binding assays, site-directed mutagenesis, HR efficiency assays, replication fork protection assays, R-loop quantification Nature Communications High 39152168
2022 Mice with a leucine-to-proline substitution at position 2431 of BRCA2 that disrupts BRCA2-DSS1 interaction lack radiation-induced RAD51 foci and show severe HR defect in somatic cells. However, mutant mice that survive are fertile with normal RAD51 recruitment during meiosis, demonstrating BRCA2-DSS1 interaction is dispensable for meiotic RAD51 loading when homologous chromosomes are in close proximity. Mouse knockin model, RAD51 foci immunofluorescence, HR reporter assay, meiosis analysis Nature Communications High 35365640
2013 Sem1 is required for the induction of SAGA-regulated genes (ARG1, GAL1) and for proper recruitment of SAGA subunits to the GAL1 promoter. Both in vivo and in vitro analyses show Sem1 influences SAGA-dependent histone H2B deubiquitylation, revealing a novel role for Sem1 (as part of TREX-2) in transcription activation and H2B deubiquitylation. Chromatin immunoprecipitation, in vitro deubiquitylation assay, transcription reporter assays Nucleic Acids Research Medium 23599000
2006 Fission yeast S. pombe Dss1 associates with the 19S regulatory particle of the 26S proteasome; dss1 mutants accumulate polyubiquitylated proteins, are sensitive to amino acid analogues, and show synthetic growth defects with other proteasome subunit mutations, establishing an evolutionarily conserved role for DSS1 in proteasome function. Co-purification, genetic suppression, polyubiquitin accumulation assay, synthetic lethality Biochemical Journal Medium 16149916
1999 S. cerevisiae SEM1 multicopy-suppresses exocyst mutants (sec3-2, sec8-9, sec10-2, sec15-1) and deletion of SEM1 rescues growth of temperature-sensitive exocyst mutants. Sem1p is mainly cytosolic but also co-sediments with the exocyst component Sec8p. SEM1 deletion triggers pseudohyphal growth in normally non-pseudohyphal diploids, and mouse Dss1 rescues this phenotype, establishing a role for SEM1 in exocytosis and cellular differentiation. Multicopy suppressor screen, temperature-sensitive growth rescue, cell fractionation, sucrose gradient co-sedimentation, pseudohyphae assay PNAS Medium 9927667
2018 In S. pombe, expanded interactome of Dss1 includes eIF3, COP9 signalosome, and mitotic septins. Dss1 forms a transient C-terminal helix that dynamically interacts with and shields a central binding region; this helix interfered with ATP-citrate lyase interaction but was required for septin binding. In dss1 deletion strains, ATP-citrate lyase solubility was reduced and septin rings were more persistent. Affinity purification-MS interactome, NMR spectroscopy, deletion strains with cellular phenotype assays Cell Reports Medium 30355493
2018 In Aspergillus nidulans, Sem1 is required for incorporation of the ubiquitin receptor Rpn10 into the 19S regulatory particle, stabilization of the Rpn11 deubiquitinating enzyme, and efficient 26S proteasome assembly. sem1 deletion strains exhibit elevated 20S proteasome activity with multiplied ATP-independent catalytic activity, maintain NADH levels, and control mitochondria integrity during stress. Genetic deletion, proteasome activity assays, co-purification, fungal development phenotyping PLOS Genetics Medium 29401458
2022 Crystal structure of the yeast Thp3186-470-Csn12-Sem1 ternary complex at 2.9 Å resolution shows Sem1 makes extensive contacts with Csn12 via a fishhook-shaped conformation to stabilize Csn12. The WH domains of Thp3 and Csn12 form a continuous nucleic acid-binding surface; mutation of basic residues in these WH domains impairs nucleic acid binding in vitro and pre-mRNA splicing in vivo. X-ray crystallography (2.9 Å), in vitro nucleic acid binding assays, site-directed mutagenesis, in vivo mRNA splicing assay Nucleic Acids Research High 35904806
2021 Human DSS1 and CSNAP have diverged in structure and function: NMR spectroscopy shows distinct structural features present in DSS1 are absent in CSNAP; DSS1 but not CSNAP binds ubiquitin, indicating they are functionally non-redundant despite both being associated with PCI complexes. NMR spectroscopy, ubiquitin binding assays Protein Science Medium 34272906
2023 S. pombe Dss1 is phosphorylated by casein kinase 2 at three threonines in its linker region; these phosphorylations do not affect ubiquitin binding but enable direct interaction with the FHA domain of the RING-FHA E3-ubiquitin ligase Dma1 in vitro. These phosphorylation sites are not conserved in human DSS1. In vitro kinase assay, NMR, FHA domain binding assays, sequence analysis Protein Science Medium 37463013
2025 Human DSS1 is an integral subunit of the Integrator-PP2A (INTAC) backbone complex. Structural analysis of DSS1-INTAC alone and in association with paused RNA Pol II shows intimate contacts between DSS1 and the INTAC backbone. Tryptophan 39 of DSS1 is critical for INTAC interaction; W39 mutation disrupts DSS1-INTAC interaction while maintaining proteasome interaction, and impairs INTAC-dependent transcriptional regulation. INTAC is identified as the major chromatin-bound form of DSS1. Structural analysis, site-directed mutagenesis (W39), co-purification, transcriptional assays Nature Communications High 40617815
2025 DSS1 interacts with LC3 and promotes its TRIM25-mediated K63-linked polyubiquitination at LC3B-K51, impairing autophagic flux, leading to p62 accumulation, TWIST1 stabilization, nuclear translocation of TWIST1, and EMT activation in renal cell carcinoma cells. Co-immunoprecipitation, ubiquitination assay, autophagy flux assay, knockdown/overexpression with phenotypic readouts Nature Communications Medium 40695833
2025 A LENG8-PCID2-SEM1 (LENG8-PS) trimer, structurally and functionally equivalent to the GANP-PCID2-SEM1 trimer of TREX-2, forms the core of a PAXT-associated TREX-2-like module. This complex competes with NPC-associated TREX-2 to determine polyadenylated RNA fate (nuclear decay vs. export) by releasing RNAs from UAP56. Biochemical reconstitution, mutagenesis, transcriptomic analysis, structural comparison bioRxiv (preprint)preprint Medium
2025 LENG8 binds to PCID2 and SEM1 to form the REX (Repressor of EXport) complex, which acts as a dominant negative factor for TREX-2 to cause RNA nuclear retention; LENG8 depletion causes misprocessed mRNAs and noncoding RNAs to leak into the cytoplasm, and LENG8 promotes RNA degradation by recruiting PAXT and the RNA exosome. Co-immunoprecipitation, RNAi/siRNA knockdown, RNA fractionation, RNA-seq bioRxiv (preprint)preprint Medium
2026 In U. maydis, Brh2 and Dss1 colocalize at DNA damage-induced foci; Dss1 recruitment to foci depends on interaction with full-length Brh2. Dss1 is required for Rad51 and Rec2 focus formation downstream of Brh2. Rad52 is required for Brh2, Rec2, and Dss1 focus formation. In avian DT40 cells, endogenously tagged DSS1 redistributes into subnuclear foci after DNA damage. Dss1 focus formation is inhibited by the proteasome inhibitor MG132 in both organisms, suggesting a role for ubiquitin in homology-directed repair. Fluorescence microscopy (GFP fusions, endogenous tagging), genetic epistasis, DNA damage sensitivity assays, proteasome inhibitor treatment DNA Repair Medium 41592391

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science (New York, N.Y.) 576 12228710
2008 A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing. Molecular cell 219 19061648
1999 Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals. Molecular and cellular biology 161 10373512
2015 Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry. Molecular cell 144 26145171
2006 DSS1 is required for the stability of BRCA2. Oncogene 105 16205630
2003 The BRCA2-interacting protein DSS1 is vital for DNA repair, recombination, and genome stability in Ustilago maydis. Molecular cell 102 14580353
2004 DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells. EMBO reports 94 15359272
2009 Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery. The Journal of cell biology 89 19289793
2004 Sem1, the yeast ortholog of a human BRCA2-binding protein, is a component of the proteasome regulatory particle that enhances proteasome stability. Journal of cell science 85 15572408
2014 Dss1 is a 26S proteasome ubiquitin receptor. Molecular cell 77 25306921
2014 The intrinsically disordered Sem1 protein functions as a molecular tether during proteasome lid biogenesis. Molecular cell 63 24412063
1998 The yeast nuclear gene DSS1, which codes for a putative RNase II, is necessary for the function of the mitochondrial degradosome in processing and turnover of RNA. Molecular & general genetics : MGG 61 9829834
2005 Brh2-Dss1 interplay enables properly controlled recombination in Ustilago maydis. Molecular and cellular biology 57 15767662
1995 The novel nuclear gene DSS-1 of Saccharomyces cerevisiae is necessary for mitochondrial biogenesis. Current genetics 56 8590460
1999 SEM1, a homologue of the split hand/split foot malformation candidate gene Dss1, regulates exocytosis and pseudohyphal differentiation in yeast. Proceedings of the National Academy of Sciences of the United States of America 49 9927667
2007 Dss1 interaction with Brh2 as a regulatory mechanism for recombinational repair. Molecular and cellular biology 44 17261595
2016 DSS1/Sem1, a Multifunctional and Intrinsically Disordered Protein. Trends in biochemical sciences 42 26944332
2008 Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation. Journal of molecular biology 40 18775730
2010 Depletion of DSS1 protein disables homologous recombinational repair in human cells. Mutation research 35 20817001
2006 Fission yeast Dss1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis. The Biochemical journal 34 16149916
2008 C. elegans dss-1 is functionally conserved and required for oogenesis and larval growth. BMC developmental biology 33 18471277
2002 Identification of Dss1 as a 12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in keratinocyte progenitor cells, with possible involvement in early skin tumorigenesis. The Journal of biological chemistry 32 12419822
2020 DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs. Nucleic acids research 29 31799622
2020 DSS1 and ssDNA regulate oligomerization of BRCA2. Nucleic acids research 28 32609828
2013 Localization of the regulatory particle subunit Sem1 in the 26S proteasome. Biochemical and biophysical research communications 27 23643786
1998 Yeast nuclear PET127 gene can suppress deletions of the SUV3 or DSS1 genes: an indication of a functional interaction between 3' and 5' ends of mitochondrial mRNAs. Acta biochimica Polonica 20 10397341
2022 BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks. Nature communications 19 35365640
2009 Dss1 regulates interaction of Brh2 with DNA. Biochemistry 19 19919104
2007 Dss1 associating with the proteasome functions in selective nuclear mRNA export in yeast. Biochemical and biophysical research communications 19 18023413
2013 Establishment and characterization of a new human extragonadal germ cell line, SEM-1, and its comparison with TCam-2 and JKT-1. Urology 17 23374840
2018 Sem1 links proteasome stability and specificity to multicellular development. PLoS genetics 13 29401458
2018 Expanded Interactome of the Intrinsically Disordered Protein Dss1. Cell reports 13 30355493
1994 Familial split hand/split foot long bone deficiency does not segregate with markers linked to the SHFD1 locus in 7q21.3-q22.1. Human molecular genetics 13 7987314
2014 Structural characterization of semen coagulum-derived SEM1(86-107) amyloid fibrils that enhance HIV-1 infection. Biochemistry 12 24811874
2013 A novel role for Sem1 and TREX-2 in transcription involves their impact on recruitment and H2B deubiquitylation activity of SAGA. Nucleic acids research 12 23599000
2021 Increased chemosensitivity via BRCA2-independent DNA damage in DSS1- and PCID2-depleted breast carcinomas. Laboratory investigation; a journal of technical methods and pathology 11 34031538
2010 Sem1: a versatile "molecular glue"? Nucleus (Austin, Tex.) 11 21327099
2024 DSS1 restrains BRCA2's engagement with dsDNA for homologous recombination, replication fork protection, and R-loop homeostasis. Nature communications 10 39152168
2023 SEM1 promotes tumor progression of glioblastoma via activating the akt signaling pathway. Cancer letters 10 37652287
2022 The anticancer effects of Metformin in the male germ tumor SEM-1 cell line are mediated by HMGA1. Frontiers in endocrinology 10 36506071
2019 Characterization of long living yeast deletion mutants that lack mitochondrial metabolism genes DSS1, PPA2 and AFG3. Gene 10 31082499
2012 Dss1 release activates DNA binding potential in Brh2. Biochemistry 10 23094644
2021 The disordered PCI-binding human proteins CSNAP and DSS1 have diverged in structure and function. Protein science : a publication of the Protein Society 9 34272906
2021 Plasma membrane-localized SEM1 protein mediates sugar movement to sink rice tissues. The Plant journal : for cell and molecular biology 9 34750914
2017 Dss1 Regulates Association of Brh2 with Rad51. Biochemistry 9 28616972
2004 BRCA2-RAD51-DSS1 interplay examined from a microbial perspective. Cell cycle (Georgetown, Tex.) 9 14726651
2022 Structural assembly of the nucleic-acid-binding Thp3-Csn12-Sem1 complex functioning in mRNA splicing. Nucleic acids research 7 35904806
2024 Regulatory elements in SEM1-DLX5-DLX6 (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits. Genetics in medicine open 5 39345948
2010 Association of the DSS1 c.143G>A polymorphism with skin squamous cell carcinoma. The Journal of investigative dermatology 4 20220765
2025 DSS1 inhibits autophagy to activate epithelial-mesenchymal transition in a pro-metastatic niche of renal cell carcinoma. Nature communications 3 40695833
2022 Conformational ensemble of amyloid-forming semenogelin 1 peptide SEM1(68-107) by NMR spectroscopy and MD simulations. Journal of structural biology 2 36191746
2021 The data of heterologous expression protocol for synthesis of 15N, 13C-labeled SEM1(68-107) peptide fragment of homo sapiens semenogelin 1. MethodsX 2 34754783
2020 DSS1 allosterically regulates the conformation of the tower domain of BRCA2 that has dsDNA binding specificity for homologous recombination. International journal of biological macromolecules 2 33011260
2025 DSS1 is required for proper Integrator-PP2A function. Nature communications 1 40617815
2023 Phosphorylation of Schizosaccharomyces pombe Dss1 mediates direct binding to the ubiquitin-ligase Dma1 in vitro. Protein science : a publication of the Protein Society 1 37463013
2015 Conformational stability of PCID2 upon DSS1 binding with molecular dynamics simulation. Journal of molecular modeling 1 25914122
2026 Dss1 facilitates Rad51 recruitment downstream of BRCA2/Brh2 in response to DNA damage. DNA repair 0 41592391
2017 A new transcript in the TCRB locus unveils the human ortholog of the mouse pre-Dß1 promoter. Immunity, inflammation and disease 0 28508570

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