Affinage

STN1

CST complex subunit STN1 · UniProt Q9H668

Length
368 aa
Mass
42.1 kDa
Annotated
2026-06-10
67 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STN1 is a core subunit of the conserved RPA-like CST (CTC1–STN1–TEN1) complex that binds single-stranded DNA via OB-fold domains and governs telomere end protection and genome-wide replication (PMID:19854130, PMID:23826127). It was first defined in budding yeast through physical and genetic interaction with Cdc13, where loss of Stn1 causes subtelomeric ssDNA accumulation and checkpoint activation (PMID:9042864), and through its negative regulation of Cdc13-mediated telomerase recruitment (PMID:11046137). STN1 partitions into separable modules: its N-terminal OB fold heterodimerizes with TEN1 in an RPA2N–RPA3-like architecture essential for telomere capping, while its C-terminal tandem winged-helix domains engage Cdc13/CTC1 and the Pol12/POLA2 subunit of DNA polymerase α-primase to limit telomerase action (PMID:19172739, PMID:20008938, PMID:23826127). At chromosome ends CTC1–STN1 terminates telomerase-mediated G-overhang extension while TEN1-assisted CST promotes C-strand fill-in by stimulating the priming and primase-to-polymerase switch of Pol α-primase through direct binding to POLA2, a stimulation STN1 can drive on its own (PMID:25503194, PMID:28934486, PMID:30026550, PMID:42148867). Beyond telomeres, STN1 is recruited to stalled replication forks following ATR–CHK1 and CaMKK2 phosphorylation of its intrinsically disordered region, where it blocks MRE11-mediated nascent-strand degradation and maintains RAD51 (PMID:34681076, PMID:38036565), and CST suppresses DSB end resection by EXO1 and BLM–DNA2 to influence repair-pathway choice and PARP-inhibitor sensitivity (PMID:40403056). STN1 additionally stabilizes CTC1 by competing with the E3 ligase TRIM32 (PMID:40923710) and carries CST-independent roles spanning base excision repair, ATM-dependent DSB repair, and R-loop-associated transcriptional activation via STAT3 and Tcf/Lef (PMID:37163605, PMID:40841373, PMID:41036624, PMID:41998405). A disease-causing STN1 mutation that selectively disrupts POLA2 binding links the Pol α-stimulating function to Coats plus–spectrum telomere pathology (PMID:28934486, PMID:29774655).

Mechanistic history

Synthesis pass · year-by-year structured walk · 31 steps
  1. 1997 High

    Established Stn1 as a telomere-associated factor by showing it binds Cdc13 and that its loss produces subtelomeric ssDNA and checkpoint activation, defining a capping rather than length-only function.

    Evidence Two-hybrid interaction, genetic suppressor screen, ssDNA detection and checkpoint analysis in budding yeast

    PMID:9042864

    Open questions at the time
    • Molecular basis of Cdc13–Stn1 binding undefined
    • No biochemical demonstration of ssDNA binding by Stn1 itself
  2. 2000 Medium

    Resolved whether Stn1 promotes or restrains telomerase, showing it is a negative regulator of Cdc13-dependent telomerase loading.

    Evidence Cdc13-Stn1 fusion overexpression and telomere length/epistasis assays in yeast

    PMID:11046137

    Open questions at the time
    • Fusion protein may not reflect endogenous regulation
    • Mechanism of telomerase exclusion not defined
  3. 2001 High

    Identified Ten1 as the third partner, establishing a three-component capping module and that Stn1–Ten1 contacts are required to restrain telomere length.

    Evidence Two-hybrid, allele-specific genetic rescue, ssDNA and checkpoint assays in yeast

    PMID:11230140

    Open questions at the time
    • Stoichiometry and structure of the trimer unknown
    • Direct DNA-binding role of each subunit unresolved
  4. 2007 High

    Showed conservation in fission yeast and that Stn1–Ten1 form an OB-fold complex independent of Pot1, positioning CST as a distinct end-protection entity.

    Evidence Gene deletion, co-IP, telomere localization and structural bioinformatics in fission yeast

    PMID:17715303

    Open questions at the time
    • OB-fold predictions not yet structurally confirmed
    • Relationship to Pol α not addressed
  5. 2008 High

    Mapped Stn1 into separable N-terminal (Ten1/capping) and C-terminal (Cdc13/Pol12/telomerase-limiting) functional domains, dissecting its dual roles.

    Evidence Truncation/domain mutagenesis, genetic complementation and ChIP in yeast

    PMID:19172739

    Open questions at the time
    • Structural interfaces unresolved
    • How Pol12 binding limits telomerase mechanistically unclear
  6. 2009 High

    Extended CST to mammals and plants, defining the human CTC1–STN1–TEN1 complex as a high-affinity sequence-independent ssDNA binder whose loss elevates telomeric G-strand ssDNA.

    Evidence Complex purification, co-IP, ssDNA-binding, siRNA/RNAi knockdown, telomere interactome proteomics across human, plant and yeast

    PMID:19648609 PMID:19854130 PMID:19854131

    Open questions at the time
    • Which subunit carries primary DNA-binding activity not yet assigned
    • Telomerase-regulation mechanism in human cells undefined
  7. 2009 Medium

    Linked Stn1 to genome-wide Pol α activity by showing its overproduction overrides the S-phase checkpoint in a Pol12-dependent manner.

    Evidence Overexpression, Rad53 activation assay, chromatin binding and pol12 genetic rescue in yeast

    PMID:19171895

    Open questions at the time
    • Overexpression phenotype may not mirror physiological role
    • Direct effect on Pol α biochemistry not shown
  8. 2009 High

    Provided the first structural framework, showing Stn1N–Ten1 adopts an RPA2N–RPA3-like fold and that disrupting this interface causes uncapping.

    Evidence X-ray crystallography of Candida Stn1N–Ten1 plus mutational telomere localization assays

    PMID:20008938

    Open questions at the time
    • Full-length trimer structure unsolved
    • C-terminal WH domain functions not structurally defined
  9. 2010 Medium

    Refined the Stn1–Ten1 interface to a specific N-terminal helix via allele-specific suppression, validating the structural model genetically.

    Evidence Structure-based mutagenesis, two-hybrid and allele-specific suppression in yeast

    PMID:20157006

    Open questions at the time
    • Single-lab genetic data
    • Interface conservation in human STN1 not tested here
  10. 2011 High

    Demonstrated that vertebrate CST specifically supports priming of DNA synthesis on ssDNA templates, connecting Stn1 directly to Pol α-primase function.

    Evidence Xenopus egg extract reconstitution with xStn1 immunodepletion and in vitro DNA synthesis assays

    PMID:22086929

    Open questions at the time
    • Direct Pol α-binding partner not yet identified
    • Telomere specificity vs general priming unresolved
  11. 2012 High

    Established that human STN1 is required for efficient lagging-strand telomere replication and modulates Pol α synthesis rather than its loading.

    Evidence shRNA knockdown, BrdU/FISH, telomere fragility and Pol α ChIP in human cells

    PMID:22964711

    Open questions at the time
    • Mechanism by which STN1 modulates Pol α activity unresolved
    • Distinction from G-strand regulation not fully defined
  12. 2012 High

    Showed Cdc13 OB2 dimerization is required for productive CST assembly and capping, adding an assembly determinant upstream of Stn1.

    Evidence Crystallography, biochemical binding and in vivo telomere length assays in yeast

    PMID:23177925

    Open questions at the time
    • Human CTC1 equivalent of OB2 dimerization not addressed
    • Single-lab structural study
  13. 2013 High

    Solved the human STN1–TEN1 structure, confirming RPA-like architecture, assigning ssDNA binding mainly to STN1, and establishing TEN1 as required for CST telomeric function.

    Evidence X-ray crystallography, in vitro ssDNA binding and cell-based telomere assays with dimerization-defective mutants

    PMID:23826127

    Open questions at the time
    • Full CTC1-containing trimer structure unsolved
    • Conformational changes on DNA binding not captured
  14. 2013 High

    Identified Cdk1 phosphorylation of Stn1 as a cell-cycle timing switch controlling CST-versus-telomerase recruitment at telomeres.

    Evidence In vitro kinase assay, phospho-site mutagenesis, ChIP and telomere length assay in yeast

    PMID:24164896

    Open questions at the time
    • Whether human STN1 is analogously regulated by Cdk1 untested here
    • Downstream effector of phospho-Stn1 unclear
  15. 2014 High

    Defined the mechanism of CST stimulation of Pol α-primase, showing purified CST/Stn1 augments primase activity and primase-to-polymerase switching via direct Pol12/POLA2 binding through both OB and WH domains.

    Evidence Fully reconstituted in vitro primase and switch assays with purified Candida CST and domain dissection

    PMID:25503194

    Open questions at the time
    • Structural basis of the Stn1–Pol12 contact not solved here
    • Coupling of stimulation to telomerase repression mechanistically separate
  16. 2014 High

    Connected shelterin to CST recruitment, showing SUMOylation of the TPP1 ortholog Tpz1 increases its affinity for Stn1 and recruits Stn1–Ten1 to inhibit telomerase.

    Evidence SUMO-site mutagenesis, SUMO-fusion binding, telomere ChIP and length assays in fission yeast, independently replicated

    PMID:24711392 PMID:24925530

    Open questions at the time
    • Whether a SUMO-TPP1–STN1 axis operates in human cells untested
    • SUMO E3 ligase responsible not pinpointed here
  17. 2014 Medium

    Established Stn1–Ten1 as the essential core capping unit able to act independently of Cdc13 under altered stoichiometry.

    Evidence Genetic epistasis with NMD pathway, Stn1 ChIP and telomere ssDNA assays in yeast

    PMID:24835988

    Open questions at the time
    • Physiological relevance of Cdc13-independent binding unclear
    • Single-lab epistasis evidence
  18. 2016 High

    Separated CST functions using an OB-fold mutant, showing short-ssDNA binding is needed for resolving endogenous replication stress and telomere duplex replication but not C-strand fill-in.

    Evidence In vitro ssDNA binding plus STN1 mutant cell-based replication assays

    PMID:27690379

    Open questions at the time
    • Molecular determinants distinguishing the two activities undefined
    • Substrate-length selectivity mechanism unresolved
  19. 2017 High

    Pinned human STN1's Pol α stimulation to its N-terminal OB fold binding POLA2's central OB fold, and showed a disease mutation selectively abolishes this, establishing clinical relevance.

    Evidence Reconstituted PP stimulation, pull-down domain mapping and disease-mutant analysis with purified human proteins

    PMID:28934486

    Open questions at the time
    • Structure of the STN1–POLA2 interface not solved
    • How POLA2 OB displacement gates the active site not visualized
  20. 2018 High

    Dissected individual CST subunit roles, showing CTC1–STN1 limits telomerase G-overhang extension while TEN1 is separately essential for C-strand synthesis and stabilizes DNA binding.

    Evidence CRISPR knockout of single subunits, overhang and telomerase ChIP and in vitro DNA binding in human cells

    PMID:29774655 PMID:30026550

    Open questions at the time
    • How TEN1 contributes to C-strand synthesis biochemically unresolved
    • Order of telomerase termination and fill-in unclear
  21. 2018 High

    Identified a SUMO-interacting motif in Stn1's C-terminus required for SUMO-Tpz1 binding and telomerase inhibition, completing the SUMO-dependent recruitment mechanism.

    Evidence SIM mutagenesis, SUMO interaction, telomere and telomerase ChIP and length assays in fission yeast

    PMID:29774234

    Open questions at the time
    • SIM conservation in mammalian STN1 not addressed
    • Relationship of SIM to DNA-binding function unclear
  22. 2021 Medium

    Identified the STN1 intrinsically disordered region as essential for replication-stress genome stability and Pol α interaction, separable from CST assembly and RAD51 binding.

    Evidence IDR mutagenesis, viability, RAD51 foci, co-IP and HU sensitivity in cells

    PMID:34681076

    Open questions at the time
    • How the IDR promotes RAD51 loading mechanistically unknown
    • Single-lab evidence
  23. 2022 Medium

    Linked yeast Stn1 to origin firing through the MCM helicase, proposing it acts as an accessory replication factor facilitating MCM activation.

    Evidence Genetic epistasis with mcm alleles, suppressor analysis and origin firing/ssDNA assays in yeast

    PMID:35150303

    Open questions at the time
    • No direct Stn1–MCM physical interaction shown
    • Conservation in human cells untested
  24. 2023 High

    Defined a phospho-regulated fork-protection role, showing ATR–CHK1 and CaMKK2 phosphorylate STN1's IDR to recruit it to stalled forks and block MRE11-mediated degradation.

    Evidence In vitro kinase assays, phospho-mutants, iPOND/fiber fork protection and MRE11/RAD51 fork ChIP

    PMID:38036565

    Open questions at the time
    • How phospho-STN1 physically excludes MRE11 unresolved
    • Interplay with CST DNA binding at forks unclear
  25. 2023 Medium

    Uncovered a non-telomeric STN1–BER axis, showing STN1 loss downregulates DNA glycosylases and causes oxidative DNA damage in colon tissue.

    Evidence Conditional STN1 knockout mouse, BER activity, glycosylase expression and oxidative damage assays

    PMID:37163605

    Open questions at the time
    • Mechanism by which STN1 controls glycosylase expression unknown
    • Direct vs indirect regulation unresolved
  26. 2025 High

    Established CST as a regulator of DSB end resection, suppressing EXO1 and BLM–DNA2 via distinct mechanisms and modulating BRCA1 status and PARP-inhibitor sensitivity.

    Evidence Biochemical resection reconstitution, CST mutant separation and cell-based PARPi resistance assays

    PMID:40403056

    Open questions at the time
    • Structural basis of CST–BLM/EXO1 contacts undefined
    • How BRCA1-BARD1 relieves only the EXO1 block unresolved
  27. 2025 Medium

    Revealed a CST-independent transcriptional role, with STN1 displacing R-loop-flanking ssDNA to recruit STAT3 and activate ZEB1, driving EMT and metastasis.

    Evidence Co-IP, ChIP, R-loop detection, ZEB1 reporter and STAT3 inhibitor rescue in pancreatic cancer models

    PMID:40841373

    Open questions at the time
    • Generality beyond PDAC unknown
    • Direct demonstration of ssDNA displacement at promoters limited
  28. 2025 Medium

    Showed STN1 stabilizes CTC1 by competing with TRIM32 for the same OB-G binding region, preventing CTC1 ubiquitination and degradation.

    Evidence Co-IP, ubiquitination assay, proteasome inhibitor rescue and AlphaFold3 modeling

    PMID:40923710

    Open questions at the time
    • Binding interface inferred from modeling not experimental structure
    • Physiological conditions triggering competition unclear
  29. 2025 Medium

    Demonstrated a CST-independent STN1–ATM axis required for both HR and NHEJ DSB repair and the G2/M checkpoint after irradiation.

    Evidence Proteomic interaction screen, ATM expression/signaling, HR/NHEJ reporter and checkpoint assays

    PMID:41036624

    Open questions at the time
    • How STN1 stabilizes ATM mechanistically unknown
    • Single-lab interaction data
  30. 2025 High

    Confirmed in human cells that STN1 limits telomerase-mediated G-overhang extension, with knockout phenotypes rescued by telomerase inhibition.

    Evidence Conditional CRISPR knockout, overhang and telomere damage assays with telomerase inhibition rescue

    PMID:42148867

    Open questions at the time
    • Molecular step at which STN1 terminates telomerase unresolved
    • Contribution of C-strand fill-in defects to instability not separated
  31. 2026 Medium

    Extended STN1's transcriptional function to germ cell development, showing it partners with Tcf/Lef to enhance Wnt/β-catenin signaling required for oocyte survival.

    Evidence Co-IP, ChIP at germ cell promoters, conditional knockout and Wnt reporter in zebrafish

    PMID:41998405

    Open questions at the time
    • Whether this role exists in mammals unknown
    • Mechanistic link between ssDNA binding and Tcf/Lef recruitment unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How STN1's many CST-independent activities (transcriptional activation, ATM stabilization, BER regulation) are coordinated with its telomeric and fork-protection roles, and whether a unified DNA/RNA-binding mechanism underlies them, remains unresolved.
  • No structure of the full CTC1–STN1–TEN1 trimer on DNA
  • Mechanistic unification of telomeric and non-telomeric functions lacking
  • Determinants directing STN1 between ssDNA, R-loops and protein partners undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 2
Pathway
R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
ATMCDC13CTC1POLA2STAT3TEN1TPP1TRIM32
Complex memberships
CST (CTC1-STN1-TEN1)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Yeast Stn1 physically interacts with Cdc13 (by two-hybrid analysis) and functions in telomere length regulation; loss of Stn1 function causes accumulation of single-stranded DNA in subtelomeric regions and activates the RAD9/MEC3 G2/M DNA damage checkpoints. Two-hybrid interaction, genetic suppressor screen, ssDNA detection assay, checkpoint genetic analysis Genes & development High 9042864
2000 Stn1 acts as an inhibitor of telomerase recruitment by Cdc13; a Cdc13-Stn1 fusion protein blocks telomere elongation, indicating Stn1 negatively regulates the telomerase-loading function of Cdc13. Fusion protein overexpression, telomere length assays, genetic epistasis Molecular and cellular biology Medium 11046137
2001 Ten1 physically associates with both Stn1 and Cdc13; a binding defect between Stn1-13 and Ten1 underlies the long-telomere phenotype; Ten1 is required for telomere length regulation and preventing single-stranded DNA accumulation at telomeres. Two-hybrid interaction, genetic complementation, ssDNA assay, checkpoint analysis The EMBO journal High 11230140
2007 Fission yeast Stn1 and Ten1 are essential for chromosome end protection and form a complex with each other but not with Pot1; they localize at telomeres in a manner correlated with ssDNA overhang length, and both contain OB-fold domains. Genetic deletion, co-immunoprecipitation, telomere localization assay, structural bioinformatics Proceedings of the National Academy of Sciences of the United States of America High 17715303
2008 Stn1 has two separable functional domains: the N-terminus interacts with Ten1 and is essential for telomere capping, while the C-terminus binds both Cdc13 and Pol12 and is required to limit continuous telomerase action. Stn1 telomere association peaks in S phase. Domain dissection/truncation analysis, genetic complementation, chromatin immunoprecipitation, in vivo binding assays The EMBO journal High 19172739
2009 Mammalian STN1 and TEN1 homologs were identified and shown to form the CST (CTC1-STN1-TEN1) complex that binds single-stranded DNA with high affinity in a sequence-independent manner; knockdown of Stn1 causes significant increases in single-stranded G-strand telomeric DNA. Protein identification, co-immunoprecipitation, ssDNA-binding assay, siRNA knockdown, telomere ssDNA quantification Molecular cell High 19854130
2009 Human OBFC1 (STN1) associates with TPP1 in the telomere interactome, localizes to telomeres in human cells, binds telomeric single-stranded DNA in vitro, and overexpression of an OBFC1 mutant results in telomere elongation. Proteomic co-immunoprecipitation, telomere localization (FISH/immunofluorescence), in vitro DNA binding assay, overexpression telomere length assay The Journal of biological chemistry Medium 19648609
2009 Crystal structure of the Candida tropicalis Stn1N-Ten1 complex shows an RPA2N-RPA3-like architecture with OB-fold packing; the C-terminal domain of S. cerevisiae Stn1 contains two WH motifs similar to RPA2-C. Mutations disrupting Stn1-Ten1 interaction cause telomere uncapping and abolish Ten1 telomere localization. X-ray crystallography, mutational analysis, telomere localization assay Genes & development High 20008938
2009 AtCTC1 (plant CTC1) physically and genetically interacts with AtSTN1; both are required for telomere integrity in Arabidopsis. Human CTC1 depletion by RNAi triggers DNA damage response and telomere defects, demonstrating conservation of the CST complex. Co-immunoprecipitation, genetic interaction, RNAi knockdown, telomere analysis Molecular cell High 19854131
2009 Overproduction of yeast Stn1 blocks S-phase checkpoint functions downstream of Rad53 activation; Stn1 broadly associates with chromosomes and its checkpoint-overriding effect depends on Pol12 (a subunit of DNA Pol α), indicating Stn1 promotes Pol α activity genome-wide when overproduced. Overexpression analysis, checkpoint kinase activation assay, chromatin binding assay, pol12 genetic rescue Proceedings of the National Academy of Sciences of the United States of America Medium 19171895
2010 Structural prediction and mutagenesis of a predicted alpha-helix in the N-terminal OB fold of S. cerevisiae Stn1 identified a specific Stn1-Ten1 interaction interface; stn1-L164D eliminates Ten1 association and is specifically suppressed by ten1-D138Y, confirming the interface. Structure-based mutagenesis, two-hybrid interaction, allele-specific suppression genetics Genetics Medium 20157006
2011 Xenopus CST (xCST) is involved in priming DNA synthesis on ssDNA templates in egg extracts; immunodepletion of xStn1 does not impair replication of chromatin DNA but specifically blocks the priming step on ssDNA templates, consistent with a role in telomeric C-strand synthesis regulation of Pol α-primase. Xenopus egg extract reconstitution, immunodepletion, in vitro DNA synthesis assay The Journal of biological chemistry High 22086929
2012 Human Stn1 depletion causes catastrophic telomere shortening and DNA damage specifically at lagging-strand telomeres; hStn1 promotes efficient replication of lagging-strand telomeric DNA, and its loss leads to persistent/elevated association of DNA Pol α with telomeres, suggesting hStn1 modulates Pol α synthesis activity rather than controlling its loading. shRNA knockdown, BrdU incorporation/FISH, telomere fragility assay, ChIP for Pol α Cell research High 22964711
2012 Cdc13 OB2 domain forms a homodimer; disruption of OB2 dimerization (e.g., by cdc13-1 mutation) impairs Cdc13-Stn1 association and causes telomere length deregulation, establishing that Cdc13 OB2 dimerization is required for proper CST assembly and productive telomere capping. X-ray crystallography, biochemical binding assay, in vivo telomere length assay, mutagenesis Structure High 23177925
2013 Crystal structure of the human STN1-TEN1 complex reveals hSTN1 with an OB domain and tandem C-terminal wHTH motifs, and hTEN1 with a single OB fold; the complex is structurally similar to RPA. hSTN1 is primarily responsible for ssDNA binding; cells expressing hSTN1 dimerization-defective mutants show elongated telomeres and telomere uncapping defects, indicating hTEN1 is required for hCST telomeric function. X-ray crystallography, in vitro ssDNA binding assay, cell-based telomere length and damage assay, mutagenesis PloS one High 23826127
2013 Cdk1 phosphorylates Stn1 at threonine 223 and serine 250 in vitro and in vivo; these phosphorylations are essential for stability of CST complexes at telomeres and regulate the temporal recruitment of CST versus telomerase complexes during the cell cycle. In vitro kinase assay, phospho-site mutagenesis, chromatin immunoprecipitation, telomere length assay Molecular and cellular biology High 24164896
2014 Purified CST from Candida glabrata substantially augments primase activity and primase-to-polymerase switching of the primase-Pol α (PP) complex; CST shortens RNA and lengthens DNA in chimeric products. Stn1 alone is sufficient for PP stimulation, acting through both its N-terminal OB fold and C-terminal WH domains via direct binding to the Pol12 subunit of PP. In vitro biochemical reconstitution with purified complexes, primase assay, primase-to-polymerase switch assay, binding assay Nature communications High 25503194
2014 SUMOylation of fission yeast shelterin subunit Tpz1 (TPP1 ortholog) on lysine 242 promotes recruitment of Stn1-Ten1 to telomeres and prevents telomerase accumulation, establishing a SUMO-dependent pathway that links shelterin to CST-mediated telomerase inhibition. SUMOylation site mutagenesis, telomere ChIP for Stn1 and telomerase, telomere length assay, SUMO-fusion protein binding assay Proceedings of the National Academy of Sciences of the United States of America High 24711392
2014 Fission yeast Tpz1 (TPP1 ortholog) SUMOylation promotes Stn1 telomere association via direct increased affinity of SUMO-Tpz1 for Stn1, independently confirmed and showing evolutionary conservation of SUMO-dependent CST recruitment. Protein interaction assay (SUMO-fusion pulldown), telomere ChIP, telomere length assay EMBO reports High 24925530
2014 Stn1 and Ten1 can function in a Cdc13-independent manner; disabling NMD alters CST stoichiometry at telomeres and permits Stn1 to bind telomeres without Cdc13, establishing Stn1 and Ten1 as the essential core of the CST capping complex. Genetic epistasis (NMD/DDR pathway mutations), ChIP for Stn1, telomere ssDNA assay Cell reports Medium 24835988
2016 An OB-fold mutation in STN1 (STN1-OBM) preferentially destabilizes binding to short ssDNA substrates and selectively impairs resolution of endogenous replication stress and telomere duplex replication in vivo, but does not affect telomeric C-strand fill-in or origin firing after exogenous replication stress, indicating mechanistic differences in CST action at different replication problems. In vitro ssDNA binding assay, STN1 mutant cell-based phenotypic analysis, telomere replication assay PLoS genetics High 27690379
2017 Human STN1 alone (purified) stimulates primase-Pol α (PP) activity in vitro primarily through its N-terminal OB fold by binding POLA2; the STN1-POLA2 interaction targets the central OB fold domain of POLA2, which in the substrate-free PP structure blocks nucleic acid entry to the Pol α active site. A disease-causing STN1 mutation selectively disrupts POLA2 binding and PP stimulation. In vitro PP stimulation assay with purified proteins, pull-down binding assay, disease mutant analysis Nucleic acids research High 28934486
2018 CTC1-STN1 together limits telomerase action to prevent G-overhang overextension; TEN1 is separately essential for C-strand synthesis. CTC1-STN1 retains ssDNA affinity without TEN1 but TEN1 stabilizes binding; CTC1-STN1 binding to DNA Pol α is required to fully repress telomerase activity. CRISPR/Cas9 knockout of individual CST subunits, telomere overhang analysis, telomerase recruitment ChIP, in vitro DNA binding assay Nature communications High 30026550
2018 CRISPR-engineered CTC1-L1142H (Coats plus mutation) disrupts CTC1-STN1 interaction, leading to telomerase-mediated telomere elongation; impaired CTC1:STN1-DNA Pol α binding further de-represses telomerase; CP CTC1 mutants failing to interact with Pol α cause loss of C-strand maintenance and catastrophic telomere shortening. CRISPR/Cas9 knock-in, co-immunoprecipitation, telomere length assay, telomerase recruitment ChIP, Pol α interaction assay Aging cell High 29774655
2018 Fission yeast Stn1 contains a SUMO-interacting motif (SIM) in its C-terminal domain that is required for interaction with SUMO and SUMO-Tpz1; SIM point mutations (Stn1-226) cause telomere elongation, impair Stn1-Ten1 recruitment to telomeres, and enhance telomerase binding, establishing the SIM as critical for telomerase inhibition at chromosome ends. SIM mutagenesis, SUMO interaction assay, telomere ChIP, telomere length assay, telomerase ChIP Science advances High 29774234
2021 The intrinsically disordered region (IDR) within the STN1 OB-fold domain is critical for maintaining genome stability under replication stress; single IDR mutations cause genome instability and reduced viability, reduce RAD51 foci under replication stress, and impair STN1-POL α interaction, without affecting CST complex formation or STN1-RAD51 direct binding. Site-directed mutagenesis, cell viability assay, RAD51 foci immunofluorescence, co-immunoprecipitation, HU sensitivity assay Biology Medium 34681076
2022 Yeast Stn1 overproduction circumvents Rad53 S-phase checkpoint through the MCM complex; Mcm2/Mcm5 mutations block Stn1-overproduction checkpoint bypass, loss-of-function stn1 mutations compensate rad53 defects, and Stn1 overproduction suppresses mcm7 mutants, indicating Stn1 functions as an accessory replication factor facilitating MCM activation at origins. Genetic epistasis, suppressor analysis, origin firing assay, ssDNA accumulation assay Current genetics Medium 35150303
2023 STN1 is phosphorylated by both ATR-CHK1 and CaMKK2 in its intrinsically disordered region in response to replication stress (hydroxyurea/aphidicolin or elevated cytosolic calcium); loss of STN1 phosphorylation reduces STN1 localization to stalled forks, elevates nascent strand degradation, increases MRE11 access, and decreases RAD51 at forks. In vitro kinase assay, phospho-site mutagenesis, fork protection assay (iPOND/fiber), MRE11/RAD51 ChIP at forks Nature communications High 38036565
2023 STN1 deficiency down-regulates multiple DNA glycosylases, resulting in defective base excision repair (BER) and accumulation of oxidative DNA damage, identifying a STN1-BER axis that protects colon tissue. Conditional STN1 knockout mouse model, BER activity assay, DNA glycosylase expression analysis, oxidative damage quantification Science advances Medium 37163605
2025 The CST complex suppresses DNA end resection by EXO1 and the BLM-DNA2 helicase-nuclease complex via distinct mechanisms; BRCA1-BARD1 alleviates the CST-imposed EXO1 blockade but has little effect on BLM-DNA2 restriction. CST mutants impaired for DNA binding or BLM-EXO1 interaction exhibit hyper-resection and render BRCA1-deficient cells resistant to PARP inhibitors. Biochemical resection assay, CST DNA-binding and protein-interaction mutant analysis, cell-based PARPi resistance assay Science (New York, N.Y.) High 40403056
2025 STN1 directly interacts with the transcription factor STAT3 and structurally displaced ssDNA flanking R-loops at gene promoters, recruiting STAT3 to activate ZEB1 transcription independently of its telomere maintenance function, thereby promoting EMT and metastasis in pancreatic cancer. Co-immunoprecipitation, ChIP, R-loop detection, ZEB1 reporter assay, STAT3 inhibitor rescue Nature communications Medium 40841373
2025 STN1 directly interacts with CTC1 at the OB-G domain and competes with TRIM32 for the same binding region; STN1 binding prevents TRIM32-mediated ubiquitination and proteasomal degradation of CTC1, thereby stabilizing the CST complex. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor rescue, structural modeling (AlphaFold3) Aging cell Medium 40923710
2025 STN1 interacts with ATM and stabilizes ATM expression and signaling after DNA damage; STN1 silencing reduces both homologous recombination and non-homologous end joining repair of DSBs and impairs G2/M checkpoint arrest after ionizing radiation, in a CST complex-independent manner. Co-immunoprecipitation/proteomic interaction screen, ATM expression/signaling assay, HR/NHEJ reporter assay, cell cycle checkpoint assay after IR Nucleic acids research Medium 41036624
2025 Conditional deletion of human STN1 causes proliferation defects, telomeric damage signaling, G-overhang overextension, and genome instability (anaphase bridges, micronuclei); these phenotypes are largely dependent on telomerase activity, establishing that STN1 limits telomerase-mediated G-overhang extension. Conditional CRISPR/Cas9 knockout, telomere overhang assay, telomere damage focus quantification, telomerase inhibition rescue Journal of cell science High 42148867
2026 In zebrafish, Stn1 interacts with the transcription factor Tcf/Lef, facilitates its association with promoters of germ cell-specific genes, and enhances Wnt/β-catenin signaling activity in oocytes; genetic deletion of stn1 leads to massive oocyte loss. Co-immunoprecipitation, ChIP at germ cell promoters, conditional genetic knockout, Wnt pathway reporter assay EMBO reports Medium 41998405

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Molecular cell 286 19854130
1997 Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes & development 238 9042864
2009 Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Molecular cell 234 19854131
2010 Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proceedings of the National Academy of Sciences of the United States of America 225 20421499
2001 Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13. The EMBO journal 213 11230140
2009 Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres. Genes & development 112 20008938
2016 Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. The Journal of experimental medicine 110 27432940
2009 OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation. The Journal of biological chemistry 109 19648609
2000 Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Molecular and cellular biology 94 11046137
2007 Protection of telomeres by a conserved Stn1-Ten1 complex. Proceedings of the National Academy of Sciences of the United States of America 91 17715303
2012 Human Stn1 protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in. Cell research 88 22964711
2008 Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition. The EMBO journal 88 19172739
2014 The CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch. Nature communications 70 25503194
2013 Structure of the human telomeric Stn1-Ten1 capping complex. PloS one 67 23826127
2019 Structural Analysis and Conformational Dynamics of STN1 Gene Mutations Involved in Coat Plus Syndrome. Frontiers in molecular biosciences 60 31245382
2018 CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells. Nature communications 58 30026550
2011 Xenopus laevis Ctc1-Stn1-Ten1 (xCST) protein complex is involved in priming DNA synthesis on single-stranded DNA template in Xenopus egg extract. The Journal of biological chemistry 57 22086929
2018 CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length. Aging cell 43 29774655
2014 SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1(Tpp1) to modulate shelterin-Stn1 interaction in fission yeast. Proceedings of the National Academy of Sciences of the United States of America 42 24711392
2017 STN1-POLA2 interaction provides a basis for primase-pol α stimulation by human STN1. Nucleic acids research 38 28934486
2016 STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST Function. PLoS genetics 35 27690379
2017 The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells. Experimental cell research 34 28366536
2003 The stn-1 syntrophin gene of C.elegans is functionally related to dystrophin and dystrobrevin. Journal of molecular biology 32 14499607
2014 Tpz1TPP1 SUMOylation reveals evolutionary conservation of SUMO-dependent Stn1 telomere association. EMBO reports 31 24925530
2013 Cdk1 regulates the temporal recruitment of telomerase and Cdc13-Stn1-Ten1 complex for telomere replication. Molecular and cellular biology 30 24164896
2012 Cdc13 OB2 dimerization required for productive Stn1 binding and efficient telomere maintenance. Structure (London, England : 1993) 30 23177925
2005 A mutation in the STN1 gene triggers an alternative lengthening of telomere-like runaway recombinational telomere elongation and rapid deletion in yeast. Molecular and cellular biology 30 16135798
2017 Fission yeast Stn1 is crucial for semi-conservative replication at telomeres and subtelomeres. Nucleic acids research 23 28180297
2015 Stn1 is critical for telomere maintenance and long-term viability of somatic human cells. Aging cell 23 25684230
2018 The fission yeast Stn1-Ten1 complex limits telomerase activity via its SUMO-interacting motif and promotes telomeres replication. Science advances 18 29774234
2017 Relationship between the TERT, TNIP1 and OBFC1 genetic polymorphisms and susceptibility to colorectal cancer in Chinese Han population. Oncotarget 18 28915643
2009 Yeast telomere capping protein Stn1 overrides DNA replication control through the S phase checkpoint. Proceedings of the National Academy of Sciences of the United States of America 18 19171895
2020 An Indian child with Coats plus syndrome due to mutations in STN1. American journal of medical genetics. Part A 17 32627942
2023 Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair. Science advances 14 37163605
2022 Pan-Cancer Analyses Identify the CTC1-STN1-TEN1 Complex as a Protective Factor and Predictive Biomarker for Immune Checkpoint Blockade in Cancer. Frontiers in genetics 13 35368664
2014 Interplay between nonsense-mediated mRNA decay and DNA damage response pathways reveals that Stn1 and Ten1 are the key CST telomere-cap components. Cell reports 13 24835988
2010 Structure prediction-driven genetics in Saccharomyces cerevisiae identifies an interface between the t-RPA proteins Stn1 and Ten1. Genetics 12 20157006
2022 Pan-cancer analysis reveals that CTC1-STN1-TEN1 (CST) complex may have a key position in oncology. Cancer genetics 11 35134616
2021 Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome. Molecular genetics & genomic medicine 11 34110109
2016 Suppression of STN1 enhances the cytotoxicity of chemotherapeutic agents in cancer cells by elevating DNA damage. Oncology letters 11 27446354
2025 CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade. Science (New York, N.Y.) 10 40403056
2023 CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection. Nature communications 10 38036565
2020 Cdc13 is predominant over Stn1 and Ten1 in preventing chromosome end fusions. eLife 9 32755541
2019 The telomeric Cdc13-Stn1-Ten1 complex regulates RNA polymerase II transcription. Nucleic acids research 9 31006804
2012 Maintenance of very long telomeres by recombination in the Kluyveromyces lactis stn1-M1 mutant involves extreme telomeric turnover, telomeric circles, and concerted telomeric amplification. Molecular and cellular biology 8 22645309
2019 Association of SNPs in the OBFC1 gene and laryngeal carcinoma in Chinese Han male population. International journal of clinical oncology 7 31016429
2023 Stn1-Ten1 and Taz1 independently promote replication of subtelomeric fragile sequences in fission yeast. Cell reports 6 37243596
2023 Pot1 promotes telomere DNA replication via the Stn1-Ten1 complex in fission yeast. Nucleic acids research 6 37953281
2022 Functional annotation and investigation of the 10q24.33 melanoma risk locus identifies a common variant that influences transcriptional regulation of OBFC1. Human molecular genetics 6 34605909
2021 Fission yeast Stn1 maintains stability of repetitive DNA at subtelomere and ribosomal DNA regions. Nucleic acids research 4 34520548
2025 STN1 facilitates metastasis by promoting transcription of EMT-activator ZEB1 in pancreatic cancer. Nature communications 3 40841373
2019 Tpz1TPP1 prevents telomerase activation and protects telomeres by modulating the Stn1-Ten1 complex in fission yeast. Communications biology 3 31396577
2025 KRAS-induced STN1 (OBFC1) promotes proper CTC1-STN1-TEN1 complex-independent DNA double-strand break repair and cell cycle checkpoint maintenance in pancreatic cancer. Nucleic acids research 2 41036624
2021 The Intrinsically Disordered Region in the Human STN1 OB-Fold Domain Is Important for Protecting Genome Stability. Biology 2 34681076
2024 Dysfunction of Telomeric Cdc13-Stn1-Ten1 Simultaneously Activates DNA Damage and Spindle Checkpoints. Cells 1 39404369
2022 Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint. Current genetics 1 35150303
2026 Stn1 promotes zebrafish oocyte development via amplifying Wnt/β-catenin signaling. EMBO reports 0 41998405
2026 Conditional deletion of human STN1 leads to telomere dysfunction, genome instability and proliferation defects. Journal of cell science 0 42148867
2026 STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation. bioRxiv : the preprint server for biology 0 42239136
2025 Drosophila telomeric protein Verrocchio is an ortholog of STN1. Genetica 0 39841234
2025 The stn1-sz2 Mutant Provides New Insight into the Impacts of Telomeric Cdc13-Stn1-Ten1 Dysfunction on Cell Cycle Progression. Cells 0 40497960
2025 In vivo investigation of STN1 downregulation in melanoma formation in adult mice following UV irradiation. bioRxiv : the preprint server for biology 0 40501869
2025 STN1 Shields CTC1 From TRIM32-Mediated Ubiquitination to Prevent Cellular Aging. Aging cell 0 40923710
2025 Stn1 supports Mec1 function in protecting stalled replication forks from degradation. PLoS genetics 0 41091836
2025 In vivo investigation of STN1 downregulation in melanoma formation in adult mice following UV irradiation. PloS one 0 41237160
2025 A Novel Biallelic STN1 Mutation Is Associated With Adult-Onset Multisystemic Involvement: Broadening the Mutational Spectrum in Coats Plus Syndrome. Clinical genetics 0 41387117
2024 Conditional Depletion of STN1 in Mouse Embryonic Fibroblasts. Bio-protocol 0 38686350

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