Affinage

SMC3

Structural maintenance of chromosomes protein 3 · UniProt Q9UQE7

Length
1217 aa
Mass
141.5 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMC3 is a core ATPase subunit of the cohesin ring that, together with SMC1, forms a constitutive heterodimer maintained at constant levels across the cell cycle and assembled with the kleisin RAD21/Scc1 and an SA1/SA2 subunit at equimolar stoichiometry into a single ring (PMID:10072753, PMID:21699228). The complex topologically engages DNA through two distinct gates: DNA enters through the Smc1–Smc3 hinge, whose passage requires the regulatory subunits Scc2 and Scc3 and is the essential gate for building sister chromatid cohesion, whereas proteolysis-independent (prophase-pathway, Wapl-dependent) release occurs through transient opening of the Smc3–kleisin interface (PMID:23361318, PMID:23340528, PMID:36094369). Cohesion establishment is directly coupled to ATP hydrolysis by the Smc1/Smc3 heads, which licenses acetylation of Smc3 at two conserved lysines (K112/K113) near the ATP-binding pocket by Eco1; this acetylation counteracts the anti-establishment activity of the Scc3–Pds5–Wapl complex and recruits sororin (PMID:19328069, PMID:25220052). A positively charged channel in the Smc1/Smc3 hinge supports the S-phase conformational change required for both acetylation and cohesion (PMID:21139566). Acetylation is reversed in anaphase by the deacetylase Hos1 (HDAC8 in human cells), regenerating a deacetylated Smc3 pool needed for the next cohesion cycle and promoting efficient sister chromatid separation by de-repressing the Smc1–Smc3 ATPase, completing an obligatory acetylation cycle (PMID:20832720, PMID:20797861, PMID:27072133, PMID:29100057). Beyond mitotic cohesion, Smc3 acetylation tunes cohesin's loop-extruding translocase activity by stabilizing Pds5 to set chromatin loop size (PMID:35710835), and SMC3-dependent genome folding controls B cell terminal differentiation and germinal-center programs, with Smc3 loss or haploinsufficiency driving lymphomagenesis (PMID:33432228). SMC3 is also a target of the DNA-damage response: it is phosphorylated by ATM/NBS1 at Ser-1083 and by CK2 at Ser-1067 to activate the intra-S checkpoint (PMID:18442975), and ATM-directed, MDC1-mediated recruitment of ESCO2 acetylates SMC3 at double-strand breaks to enable 53BP1 recruitment (PMID:37377435). CdLS-associated hinge mutations alter SMC3–DNA dynamics and confer genomic instability (PMID:18996922).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 Medium

    Establishing the molecular identity of SMC3 was the first step: cloning revealed a five-domain head-rod-tail SMC architecture with coiled-coil rod, defining the protein later recognized as a cohesin subunit.

    Evidence Full-length cDNA cloning, secondary structure prediction, and immunochemical confirmation (bamacan/SMC3)

    PMID:10358101 PMID:9015313

    Open questions at the time
    • Cloning did not establish chromosomal/cohesin function
    • Reported basement-membrane CSPG/proteoglycan attributes not reconciled with later cohesin biology
  2. 1999 Medium

    Defining SMC3 as one half of a constitutive SMC1–SMC3 heterodimer with DNA-binding and recombination activity placed it in a chromosomal complex.

    Evidence Recombinant complex purification (RC-1), in vitro DNA-binding/ring-closure assays, cell-cycle Western blots and immunofluorescence

    PMID:10072753 PMID:10608896

    Open questions at the time
    • DNA-binding mapped on isolated domains, not intact ring
    • Topological entrapment vs. direct binding not distinguished
  3. 2008 High

    Identifying ATM/NBS1- and CK2-dependent phosphorylation of SMC3 connected the subunit to the intra-S phase DNA-damage checkpoint, extending its role beyond cohesion.

    Evidence In vivo phospho-site mapping (S1067, S1083), kinase knockdown, site-directed mutagenesis, intra-S checkpoint assays

    PMID:18442975

    Open questions at the time
    • Downstream effectors of phosphorylated SMC3 in checkpoint not defined
    • Structural consequence of S1083 phosphorylation unknown
  4. 2009 High

    Discovery that Eco1 acetylates Smc3 at K112/K113 and that this counteracts the Scc3–Pds5–Wapl anti-establishment activity revealed the molecular switch for cohesion establishment.

    Evidence Yeast suppressor genetics, MS acetylation-site mapping, epistasis analysis

    PMID:19328069

    Open questions at the time
    • How acetylation near the ATP pocket inhibits release not structurally resolved
    • Direct biochemical link to sororin not yet shown at this stage
  5. 2010 High

    Identifying Hos1 as the Smc3 deacetylase that acts at anaphase established an acetylation/deacetylation cycle coupling cohesion establishment to chromosome-cycle progression.

    Evidence HDAC deletion screen, Co-IP, in vitro deacetylation, active-site mutagenesis, cohesion assays in yeast

    PMID:20797861 PMID:20832720 PMID:20832721

    Open questions at the time
    • How Hos1 is restricted to dissociated cohesin not fully defined
    • Mammalian equivalent not yet identified at this point
  6. 2010 High

    Crystallizing the Smc1/Smc3 hinge and showing a positively charged channel essential for acetylation linked hinge architecture to the S-phase conformational change required for cohesion.

    Evidence Mouse hinge crystal structure plus charge-neutralizing mutagenesis with acetylation/chromosome-association readouts in yeast

    PMID:21139566

    Open questions at the time
    • Nature of the conformational change in the intact ring not visualized
    • Mechanistic link between channel charge and head-domain acetylation indirect
  7. 2013 High

    Domain-locking experiments resolved that the Smc3–kleisin interface is the exit gate for proteolysis-independent (Wapl-dependent) release, distinct from the Smc1–Smc3 hinge used for DNA entry.

    Evidence Translational fusion of Smc3 C-terminus to kleisin N-terminus with functional/imaging readouts in human and Drosophila cells

    PMID:23340528 PMID:23361318

    Open questions at the time
    • Did not define the structural trigger for gate opening
    • Whether entry strictly requires hinge in all contexts left open
  8. 2013 Medium

    Single-molecule manipulation showed the SMC1–SMC3 heterodimer alone compacts DNA into loops in an ATP-independent, supercoiling- and hinge-dependent manner, implicating the heterodimer in DNA organization.

    Evidence Optical/magnetic tweezers with recombinant yeast SMC1–SMC3 and hinge mutants

    PMID:23620281

    Open questions at the time
    • Relationship of this ATP-independent compaction to ATP-dependent loop extrusion unclear
    • Done without kleisin/HEAT subunits
  9. 2014 High

    Demonstrating that ATP hydrolysis by the Smc1/Smc3 heads is directly required for Smc3 acetylation, sororin recruitment, and cohesion coupled DNA entrapment to cohesion establishment.

    Evidence ATPase-site mutagenesis with ChIP, acetylation, sororin-interaction, and cohesion assays in human cells

    PMID:25220052

    Open questions at the time
    • Order of head engagement, hydrolysis, and acetylation not fully resolved
    • Structural state of the acetylated head not defined
  10. 2016 Medium

    Identifying HDAC8 as the human SMC3 deacetylase extended the yeast Hos1 acetylation cycle to mammalian cells and linked it to proliferation and survival.

    Evidence HDAC8 inhibitor (PCI-34051), acetylation Western blots, siRNA, ER ChIP, cell-cycle/apoptosis assays in MCF7 cells

    PMID:27072133

    Open questions at the time
    • Inhibitor effects vs. direct catalysis not fully separated
    • Whether HDAC8 acts only on dissociated cohesin in human cells unresolved
  11. 2017 High

    Conditional Hos1 depletion showed Smc3 deacetylation is needed for efficient anaphase sister separation, not merely Smc3 recycling, likely by de-repressing Smc1–Smc3 ATPase-driven head disengagement.

    Evidence Auxin-inducible Hos1 degron, live-cell imaging, cohesin ChIP, Scc1 cleavage assays in yeast

    PMID:29100057

    Open questions at the time
    • Direct demonstration that deacetylation stimulates ATPase not shown biochemically
    • Coupling to Wapl pathway during anaphase not fully resolved
  12. 2022 High

    Reconstituted entrapment and Hi-C experiments confirmed the hinge as the essential DNA entry gate and showed Smc3 acetylation tunes loop-extruding translocase activity via Pds5 stabilization, integrating acetylation with genome folding.

    Evidence In vitro DNA entrapment with mutant cohesin, interface-locking and lethality tests, Hi-C with acetylation mutants and Pds5/Scc2 depletion in yeast

    PMID:35710835 PMID:36094369

    Open questions at the time
    • Molecular geometry of DNA passage through hinge not directly visualized
    • How acetylation-stabilized Pds5 mechanically restrains translocation unresolved
  13. 2021 High

    In vivo Smc3 deletion and haploinsufficiency in B cells showed SMC3-dependent genome folding controls germinal-center differentiation programs and constrains lymphomagenesis, defining a dosage-sensitive developmental/tumor-suppressive role.

    Evidence Conditional homozygous/heterozygous Smc3 deletion in mice with Hi-C, RNA-seq, ATAC-seq, and lymphoma models

    PMID:33432228

    Open questions at the time
    • Direct loops linking SMC3 to Bcl6/Tet2/Kmt2d loci not all mapped
    • Mechanism of dosage sensitivity not defined
  14. 2023 Medium

    Defining an ATM→ESCO2→SMC3-acetylation axis at double-strand breaks showed acetylated SMC3 stabilizes cohesin conformation to enable 53BP1 recruitment, integrating SMC3 acetylation into DSB repair architecture.

    Evidence Phospho-site MS, Co-IP, ChIP, ATM inhibition, ESCO2 mutagenesis, 53BP1 imaging, xenografts

    PMID:37377435

    Open questions at the time
    • Single-lab pathway awaits independent confirmation
    • How SMC3 acetylation geometrically promotes 53BP1 microdomain formation unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SMC3's mitotic cohesion role, its ATP-independent DNA-compaction and loop-extrusion activities, its DNA-damage phosphorylation/acetylation, and reported non-chromosomal localizations (ciliary, basement-membrane) are mechanistically unified remains unresolved.
  • No structural model reconciling DNA-damage modifications with the cohesion cycle
  • Functional significance of ciliary/RPGR and meiotic SC associations not mechanistically integrated
  • Reported proteoglycan attributes not reconciled with cohesin biology

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0005198 structural molecule activity 3 GO:0140657 ATP-dependent activity 3
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 2
Partners
ESCO2HDAC8PDS5RAD21SCC3SMC1WAPL
Complex memberships
cohesin

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Smc3 is acetylated by the acetyltransferase Eco1 at two conserved lysine residues (K112 and K113) near its ATP-binding pocket during S phase, and this acetylation promotes sister chromatid cohesion establishment by counteracting an antiestablishment activity mediated by the Scc3-Pds5-Rad61 (Wapl) complex. Mutations at K112/K113 (to arginine) cause lethality that is suppressed by mutations in scc3, pds5, and rad61, establishing genetic epistasis. Yeast genetics (suppressor mutations), acetylation site identification by mass spectrometry, epistasis analysis Molecular cell High 19328069
2010 Smc3 acetylation by Eco1 is reversed at anaphase by the class I histone deacetylase Hos1 in budding yeast. Cohesin is protected from deacetylation while bound to chromosomes but is deacetylated upon dissociation at anaphase onset. Non-acetylated Smc3 is required as a substrate for cohesion establishment in the subsequent S phase, demonstrating an Smc3 acetylation cycle essential for the chromosome cycle. Histone deacetylase deletion screen, co-immunoprecipitation (Hos1–Smc3 interaction), Hos1 overexpression/active-site mutagenesis, cohesion assays Molecular cell High 20797861 20832720
2010 Hos1 is a lysine deacetylase for the Smc3 subunit of cohesin in S. cerevisiae, identified by screening nine histone deacetylase deletion strains. Hos1 interacts with Smc3 (Co-IP, most pronounced at anaphase), directly deacetylates Smc3, and maintains a soluble pool of deacetylated Smc3 needed for the next cohesion cycle. Overexpression of Hos1 reduces Smc3 acetylation and causes cohesion defects; active-site mutation abolishes these defects. Deletion screen of nine HDACs, co-immunoprecipitation, in vitro deacetylation assay, active-site mutagenesis, cohesion assays Current biology : CB High 20797861
2010 An acetylation cycle of Smc3's nucleotide-binding domain (NBD) is essential for cohesion establishment. Smc3 molecules that remain acetylated after mitosis (due to Hos1 inactivation) cannot generate cohesion in the next S phase. Conversely, inducing Smc3 deacetylation in post-replicative cells by Hos1 overexpression reduces cohesion, providing evidence that Smc3 acetylation also contributes to cohesion maintenance. Conditional deacetylase overexpression (Hos1), cohesion establishment assays, acetylation state monitoring Molecular cell High 20832721
2014 Cohesin's ATPase activity (Smc1/Smc3) is required not only for DNA loading but also directly for Smc3 acetylation. Human cohesin ATPase mutants associate transiently with DNA but cannot be acetylated on Smc3, fail to recruit sororin, and do not mediate cohesion. The absence of Smc3 acetylation in ATPase mutants is directly caused by inability to hydrolyze ATP, not merely by transient DNA association, coupling DNA entrapment to cohesion establishment. ATPase site mutagenesis, chromatin immunoprecipitation, acetylation assays, sororin interaction assays, cohesion assays in human cells Current biology : CB High 25220052
2013 Proteolysis-independent (prophase pathway) removal of human cohesin from chromosome arms requires dissociation of Smc3 from Scc1 (opening of the Smc3–kleisin gate), but not opening of the Smc1–Smc3 hinge gate. Conversely, cohesin loading onto chromatin in telophase occurs through the Smc1–Smc3 hinge, establishing that DNA entry and exit use distinct gates of the cohesin ring. Translational fusion (Smc3 C-terminus fused to kleisin N-terminus) to lock gate, functional assays in human cells, epistasis with Wapl The EMBO journal High 23340528 23361318
2013 Wapl-dependent release of cohesin from Drosophila polytene chromosomes (interphase) and neuroblast chromosome arms (prophase) is blocked by covalently fusing Smc3's C-terminus to kleisin's N-terminus, demonstrating that proteolysis-independent cohesin release requires transient dissociation of the Smc3/kleisin interface (exit gate), which is distinct from the Smc1/Smc3 hinge used for DNA entry. Translational fusion (Smc3–kleisin) in Drosophila, live-cell and polytene chromosome imaging, genetic epistasis with Wapl The EMBO journal High 23340528
2022 Cohesin possesses two distinct DNA gates: one at the Smc3/Scc1 interface (used for separase-independent exit) and a second at the Smc1/Smc3 hinge (essential for building sister chromatid cohesion). Passage through the hinge requires regulatory subunits Scc2 and Scc3, and locking the hinge (but not the Smc3/Scc1 interface) is lethal in vivo, indicating the hinge gate is the essential DNA entry gate for cohesion. In vitro DNA entrapment assays with mutant cohesin, interface-locking experiments, genetic lethality tests in yeast eLife High 36094369
2008 SMC3 is phosphorylated in vivo at Ser-1083 in an ionizing radiation (IR)-inducible, ATM- and NBS1-dependent manner, and this phosphorylation is required for the intra-S phase checkpoint. SMC3 is also constitutively phosphorylated at Ser-1067 by CK2; Ser-1067 phosphorylation modulates Ser-1083 phosphorylation, and CK2 knockdown attenuates both Ser-1067 phosphorylation and the intra-S checkpoint. In vivo phosphorylation mapping, siRNA knockdown (ATM, NBS1, CK2), phospho-specific antibodies, intra-S checkpoint assays, site-directed mutagenesis (S1067A) The Journal of biological chemistry High 18442975
2008 CdLS-associated missense mutations in the SMC3 (and SMC1A) hinge domains cause higher affinity DNA binding compared to wild-type proteins, and CdLS cell lines with these mutations display genomic instability and sensitivity to ionizing radiation and interstrand crosslinking agents, indicating that mutations alter the dynamic association between SMC proteins and DNA. Recombinant hinge domain pulldown/binding assays (wild-type vs mutant), DNA damage sensitivity assays in patient-derived cell lines Human molecular genetics Medium 18996922
2010 The Smc1/Smc3 hinge contains a positively charged channel (defined by crystal structure of the Mus musculus hinge) and mutations in yeast Smc1 and Smc3 that together neutralize this channel's charge are lethal, reduce Smc3 acetylation during replication, and have little effect on dimerization or chromosome association, suggesting the positively charged channel is involved in a conformational change during S phase required for cohesion. Crystal structure of Mus musculus Smc1/Smc3 hinge, charge-neutralizing mutagenesis in yeast, acetylation assays, chromosome association assays The EMBO journal High 21139566
1999 The SMC3 C-terminal domain and coiled-coil region both bind double-stranded DNA, preferring duplex and secondary-structure DNAs; the N-terminus is inactive for DNA binding. Unlike cruciform DNA-binding proteins (e.g., HMG1), the SMC3 C-terminal and coiled-coil domains do not bend DNA but prevent bending (ring closure assays). Neither domain blocks DNA ends from enzymatic access. In vitro DNA-binding assays with recombinant SMC3 domain fragments, ring closure (ligation) assays, phosphatase/exonuclease/ligase accessibility assays The Journal of biological chemistry Medium 10608896
2013 The purified budding yeast SMC1-SMC3 cohesin heterodimer compacts DNA molecules by forming loops (~130 nm extension steps) against applied forces up to 0.45 pN. This compaction is dependent on DNA supercoiling (positive torsional stress preferred) and does not require ATP, but depends on the dimerization hinge region of the heterodimer. Single-molecule DNA manipulation (optical tweezers/magnetic tweezers), recombinant SMC1-SMC3 heterodimer, hinge-mutant proteins Nucleic acids research Medium 23620281
2000 Mammalian SMC1 and SMC3 co-localize in a beaded pattern along the axial elements of synaptonemal complexes in pachytene and diplotene spermatocytes, and both proteins are enriched in purified synaptonemal complex preparations and interact with SC-specific proteins SCP2 and SCP3 by multiple experimental approaches. Immunofluorescence on testis sections and spermatocyte spreads, fractionation/enrichment of synaptonemal complexes, co-immunoprecipitation with SCP2 and SCP3 Journal of cell science Medium 10652260
2003 Meiotic cohesin REC8 forms axial element-like structures before SMC1beta, SMC3, SCP2, and SCP3 are incorporated. Subsequently SMC3 (with other proteins) forms dots along REC8-AEs that extend to line the full AE. In metaphase I, SMC3 disappears from chromosome arms and concentrates around centromeres until anaphase II. RAD51/DMC1 co-immunoprecipitates with REC8, indicating distinct roles for REC8 vs. SMC3 in meiotic arm cohesion. Immunofluorescence time-course on rat spermatocyte spreads, co-immunoprecipitation, fractionation The Journal of cell biology Medium 12615909
2005 RPGR-ORF15 (retinitis pigmentosa GTPase regulator) interacts with SMC1 and SMC3 in the retinal axoneme; this interaction is mediated at least in part by the RCC1-like domain of RPGR and was not observed with phosphorylation-deficient SMC1 mutants. SMC1 and SMC3 localize to cilia of retinal photoreceptors and MDCK cells, indicating a non-chromosomal function of SMC3 in ciliary compartments. Mass spectrometry of anti-ORF15 immunoprecipitates from axoneme fraction, pulldown assays with recombinant domains, immunofluorescence localization The Journal of biological chemistry Medium 16043481
1999 Bovine SMC1 and SMC3 are the subunits of the DNA recombination complex RC-1 that catalyzes DNA transfer reactions. Both proteins contain hallmark SMC family features (P-loop, DA-box, coiled-coil) and form a constitutive heterodimer present at roughly constant levels throughout the cell cycle. Immunofluorescence shows SMC1 in chromatin-associated foci that dissolve during M phase. cDNA cloning and sequencing, recombinant complex purification, immunofluorescence, Western blotting across cell cycle stages Gene Medium 10072753
2006 SMC3 knockdown in human cells and antisense-mediated loss of Smc3 in zebrafish triggers p53-dependent apoptosis (via p53 and its target Bax), genomic instability (aneuploidy in zebrafish, centrosome amplification in human cells), and morphological malformations in developing tail/notochord. The apoptosis and phenotype are suppressed by p53 morpholino in zebrafish, demonstrating a p53-dependent mitotic checkpoint response to SMC3 deficiency. siRNA knockdown (human cells), antisense morpholino (zebrafish), p53 MO rescue, flow cytometry (centrosome, aneuploidy), apoptosis assays Molecular cancer Medium 17081288
2000 Overexpression of full-length bamacan/SMC3 in NIH and Balb/c 3T3 fibroblasts causes foci of transformation and anchorage-independent growth, demonstrating that deregulated SMC3 expression is sufficient to drive cell transformation. The same 3–4-fold overexpression is detected in ~70% of human colon carcinoma specimens. Stable transfection of full-length SMC3 cDNA in murine fibroblasts, focus-formation assay, soft-agar anchorage-independent growth, Western blotting of patient tumor specimens The Journal of biological chemistry Medium 10801778
2003 The SMC3 promoter contains functional beta-catenin/TCF4 binding sites (at -48 bp and -701 bp). Beta-catenin/TCF4 complexes from colon carcinoma nuclear extracts bind these sequences (EMSA/supershift), and co-transfection of beta-catenin enhances SMC3 promoter activity, while E-cadherin represses it, establishing SMC3 as a transcriptional target of the Wnt/beta-catenin pathway. Reporter gene (luciferase) transfections with promoter deletions/mutations, EMSA and supershift assays, beta-catenin co-transfection The Journal of biological chemistry Medium 12651860
2016 HDAC8 is the deacetylase responsible for removing SMC3 acetylation after anaphase in human (MCF7) cells. Inhibition of HDAC8 with PCI-34051 causes accumulation of acetylated SMC3 but does not affect estrogen-responsive cohesin-dependent transcription; instead it delays cell cycle progression, suppresses proliferation, and induces apoptosis in a concentration-dependent manner. HDAC8-specific inhibitor (PCI-34051), acetylation Western blotting, siRNA knockdown of RAD21/SMC3, estrogen receptor ChIP, cell cycle analysis, apoptosis assays The Journal of biological chemistry Medium 27072133
2017 Smc3 deacetylation by Hos1 is required for efficient sister chromatid separation in early anaphase in budding yeast, beyond simply recycling Smc3 for the next cycle. Hos1 depletion delays sister chromatid separation and segregation without altering Scc1 cleavage efficiency. Deacetylation promotes cohesin removal from chromosomes, likely by de-repressing Smc1-Smc3 ATPase activity (disengagement of Smc1-Smc3 heads). Conditional Hos1 depletion (auxin-inducible degron), live-cell imaging of sister chromatid separation, cohesin ChIP, Scc1 cleavage assays Molecular cell High 29100057
2022 Smc3 acetylation during S phase counteracts the loop-expanding translocase activity of cohesin by stabilizing Pds5, which finely tunes chromatin loop size and stability in G2. The cohesin loader Scc2, which stimulates cohesin ATPase activity, is also essential for cohesin translocation and loop expansion in vivo. Hi-C chromatin conformation capture in yeast, Smc3 acetylation mutants, Pds5 and Scc2 conditional depletion, loop size quantification Nature structural & molecular biology High 35710835
2023 In response to DNA double-strand breaks, ATM phosphorylates ESCO2 at S196 and T233; MDC1 recognizes phospho-ESCO2 and recruits it to DSB sites, where ESCO2-mediated acetylation of SMC3 stabilizes cohesin complex conformation and regulates chromatin structure at breaks, which is essential for 53BP1 recruitment and formation of 53BP1 microdomains. Mass spectrometry (phosphorylation site mapping), Co-IP, chromatin immunoprecipitation, ATM inhibitor/mutant analysis, ESCO2 knockdown/mutagenesis, 53BP1 foci imaging, xenograft model Nucleic acids research Medium 37377435
1997 Bamacan (SMC3) was cloned in full and found to have a five-domain head-rod-tail configuration; the rod region forms coiled-coil structures. The protein carries N-linked oligosaccharides and chondroitin sulfate chains attached at domain junctions. Antibodies to fusion proteins stained basement membranes and immunoprecipitated in vitro-translated bamacan, confirming identity of the cloned protein as the basement membrane CSPG core protein. Full-length cDNA cloning and sequencing, secondary structure prediction, in vitro transcription/translation followed by immunoprecipitation, immunohistochemistry The Journal of cell biology Medium 9015313
1999 The mouse Bamacan gene was fully cloned; its protein product has sequential globular domains connected by alpha-helical coiled-coils with N- and C-terminal P-loop and DA-box motifs consistent with ATP binding, classifying Bamacan as an SMC family member (SMC3). The gene comprises 31 exons, maps to distal chromosome 19 (syntenic to human 10q25), is driven by a GC-rich TATA-less promoter with Jun/Fos elements (-659 to -481 bp), and is constitutively overexpressed in transformed cells. Genomic cloning, exon mapping, promoter deletion/reporter assays, FISH mapping, RT-PCR expression profiling The Journal of biological chemistry Medium 10358101
2011 Quantitative mass spectrometry (qConCAT-based isotope labeling) showed that the endogenous vertebrate cohesin core complex (SMC1, SMC3, RAD21, SA1/SA2) contains equimolar amounts of all four subunits, supporting the single-ring model in which one SMC3 molecule participates per cohesin ring. Quantitative mass spectrometry (qConCAT isotope dilution) of endogenous cohesin immunoprecipitates Journal of proteome research Medium 21699228
2021 Homozygous deletion of Smc3 in B cells abrogates germinal center (GC) formation entirely, while Smc3 haploinsufficiency leads to GC hyperplasia, impaired plasma cell differentiation, and acceleration of lymphomagenesis with constitutive Bcl6 expression. Genome-wide chromosomal conformation profiling showed defects in GC B cell terminal differentiation programs controlled by epigenetic tumor suppressors Tet2 and Kmt2d, and failure to switch from B cell- to PC-defining transcription factor programs. Conditional homozygous/heterozygous Smc3 deletion in mice (Cre-lox), Hi-C, RNA-seq, ATAC-seq, flow cytometry, lymphoma mouse models Nature immunology High 33432228
2009 RNAi-mediated depletion of SMC3 in Trypanosoma brucei interferes with faithful mitotic segregation of large chromosomes but has no visible effect on minichromosome segregation. SMC3 associates with chromatin only between G1 and metaphase and is soluble throughout the rest of the cell cycle. RNAi depletion, in situ hybridization (chromosome segregation), cell fractionation (soluble vs. chromatin-bound) Molecular microbiology Low 19183276
2013 siRNA knockdown of human SMC1 causes SMC3 to accumulate in the cytoplasm and remain stable but not associate with other cohesin proteins, while SMC3 knockdown renders SMC1 unstable without cytoplasmic accumulation. FRAP experiments confirm that excess nuclear SMC3 after SMC1 depletion is highly mobile and not stably chromosome-associated. Paucity of either SMC protein causes RAD21 degradation. siRNA knockdown, subcellular fractionation, FRAP, Western blotting, rescue with bovine/mouse EGFP-tagged SMC proteins PloS one Medium 23776448

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. American journal of human genetics 416 17273969
2003 A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell. Development (Cambridge, England) 370 12571107
2003 Dpp signaling silences bam transcription directly to establish asymmetric divisions of germline stem cells. Current biology : CB 346 14561403
2009 Membrane protein architects: the role of the BAM complex in outer membrane protein assembly. Nature reviews. Microbiology 297 19182809
1984 Enzymatic restriction of mammalian cell DNA using Pvu II and Bam H1: evidence for the double-strand break origin of chromosomal aberrations. International journal of radiation biology and related studies in physics, chemistry, and medicine 275 6086544
1995 Structure of Bam HI endonuclease bound to DNA: partial folding and unfolding on DNA binding. Science (New York, N.Y.) 274 7624794
2011 β-Barrel membrane protein assembly by the Bam complex. Annual review of biochemistry 268 21370981
2009 Building sister chromatid cohesion: smc3 acetylation counteracts an antiestablishment activity. Molecular cell 267 19328069
2016 Structural basis of outer membrane protein insertion by the BAM complex. Nature 252 26901871
2003 Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3. The Journal of cell biology 226 12615909
1997 Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells. Development (Cambridge, England) 209 9342057
2011 The Bam machine: a molecular cooper. Biochimica et biophysica acta 150 21893027
2010 An Smc3 acetylation cycle is essential for establishment of sister chromatid cohesion. Molecular cell 144 20832721
2005 RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. The Journal of biological chemistry 144 16043481
2009 Bam and Bgcn antagonize Nanos-dependent germ-line stem cell maintenance. Proceedings of the National Academy of Sciences of the United States of America 140 19470484
2020 Structure of a nascent membrane protein as it folds on the BAM complex. Nature 134 32528179
1983 Size and structure of the highly repetitive BAM HI element in mice. Nucleic acids research 130 6308571
2008 BAM receptors regulate stem cell specification and organ development through complex interactions with CLAVATA signaling. Genetics 129 18780746
2000 Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes. Journal of cell science 122 10652260
1994 T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death. Journal of immunology (Baltimore, Md. : 1950) 113 7907632
2010 Hos1 deacetylates Smc3 to close the cohesin acetylation cycle. Molecular cell 97 20832720
1986 An Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA5) partly encoded by the transformation-associated Bam WYH region of EBV DNA: preferential expression in lymphoblastoid cell lines. Proceedings of the National Academy of Sciences of the United States of America 95 3018741
2008 Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA. Human molecular genetics 93 18996922
2013 Prophase pathway-dependent removal of cohesin from human chromosomes requires opening of the Smc3-Scc1 gate. The EMBO journal 92 23361318
2010 Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes. Human reproduction (Oxford, England) 89 20634189
2009 eIF4A controls germline stem cell self-renewal by directly inhibiting BAM function in the Drosophila ovary. Proceedings of the National Academy of Sciences of the United States of America 82 19556547
2011 The crystal structure of BamB suggests interactions with BamA and its role within the BAM complex. Journal of molecular biology 79 21277859
1999 Identification of TER94, an AAA ATPase protein, as a Bam-dependent component of the Drosophila fusome. Molecular biology of the cell 76 10564274
2018 The WD40 Protein BamB Mediates Coupling of BAM Complexes into Assembly Precincts in the Bacterial Outer Membrane. Cell reports 75 29847806
2014 Cohesin's ATPase activity couples cohesin loading onto DNA with Smc3 acetylation. Current biology : CB 74 25220052
2023 Structural basis of BAM-mediated outer membrane β-barrel protein assembly. Nature 72 37100902
2013 Disengaging the Smc3/kleisin interface releases cohesin from Drosophila chromosomes during interphase and mitosis. The EMBO journal 72 23340528
2015 De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes. Human mutation 71 25655089
2010 Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome. American journal of medical genetics. Part A 71 20358602
2018 Hydrogen gas inhibits lung cancer progression through targeting SMC3. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 67 29852353
2019 Alfred: interactive multi-sample BAM alignment statistics, feature counting and feature annotation for long- and short-read sequencing. Bioinformatics (Oxford, England) 66 30520945
2013 Mei-p26 cooperates with Bam, Bgcn and Sxl to promote early germline development in the Drosophila ovary. PloS one 66 23526974
1996 Perlecan and basement membrane-chondroitin sulfate proteoglycan (bamacan) are two basement membrane chondroitin/dermatan sulfate proteoglycans in the Engelbreth-Holm-Swarm tumor matrix. The Journal of biological chemistry 66 8621634
2010 A positively charged channel within the Smc1/Smc3 hinge required for sister chromatid cohesion. The EMBO journal 65 21139566
2005 Pelota controls self-renewal of germline stem cells by repressing a Bam-independent differentiation pathway. Development (Cambridge, England) 64 16280348
2008 Regulation of intra-S phase checkpoint by ionizing radiation (IR)-dependent and IR-independent phosphorylation of SMC3. The Journal of biological chemistry 62 18442975
2010 Hos1 is a lysine deacetylase for the Smc3 subunit of cohesin. Current biology : CB 60 20797861
2010 A modular BAM complex in the outer membrane of the alpha-proteobacterium Caulobacter crescentus. PloS one 57 20062535
1999 Localization and function of Bam protein require the benign gonial cell neoplasm gene product. Developmental biology 57 10433830
2000 Overexpression of bamacan/SMC3 causes transformation. The Journal of biological chemistry 55 10801778
2016 The TamB ortholog of Borrelia burgdorferi interacts with the β-barrel assembly machine (BAM) complex protein BamA. Molecular microbiology 53 27588694
2018 Long Noncoding RNA Meg3 Regulates Mafa Expression in Mouse Beta Cells by Inactivating Rad21, Smc3 or Sin3α. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 52 29529600
2017 Bam-dependent deubiquitinase complex can disrupt germ-line stem cell maintenance by targeting cyclin A. Proceedings of the National Academy of Sciences of the United States of America 52 28484036
2013 The SMC1-SMC3 cohesin heterodimer structures DNA through supercoiling-dependent loop formation. Nucleic acids research 52 23620281
2022 Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin-dependent chromatin loops. Nature structural & molecular biology 50 35710835
2016 HDAC8 Inhibition Blocks SMC3 Deacetylation and Delays Cell Cycle Progression without Affecting Cohesin-dependent Transcription in MCF7 Cancer Cells. The Journal of biological chemistry 50 27072133
2018 Hitting with a BAM: Selective Killing by Lectin-Like Bacteriocins. mBio 44 29559575
2006 SMC3 knockdown triggers genomic instability and p53-dependent apoptosis in human and zebrafish cells. Molecular cancer 44 17081288
2020 Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis. eLife 43 33146611
1999 Mammalian SMC3 C-terminal and coiled-coil protein domains specifically bind palindromic DNA, do not block DNA ends, and prevent DNA bending. The Journal of biological chemistry 40 10608896
2021 Bacterial Outer Membrane Proteins Are Targeted to the Bam Complex by Two Parallel Mechanisms. mBio 39 33947759
2016 Classifying β-Barrel Assembly Substrates by Manipulating Essential Bam Complex Members. Journal of bacteriology 39 27161117
1999 Cloning and characterization of mammalian SMC1 and SMC3 genes and proteins, components of the DNA recombination complexes RC-1. Gene 39 10072753
2021 The role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding. Nature communications 38 34234105
2019 The big BAM theory: An open and closed case? Biochimica et biophysica acta. Biomembranes 36 31520605
1997 cDNA cloning of the basement membrane chondroitin sulfate proteoglycan core protein, bamacan: a five domain structure including coiled-coil motifs. The Journal of cell biology 36 9015313
2023 Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E. coli Cells. Angewandte Chemie (International ed. in English) 34 37162386
2021 Smc3 dosage regulates B cell transit through germinal centers and restricts their malignant transformation. Nature immunology 33 33432228
2009 Investigation of the role of the BAM complex and SurA chaperone in outer-membrane protein biogenesis and type III secretion system expression in Salmonella. Microbiology (Reading, England) 33 19372159
2019 The Significant Reduction or Complete Eradication of Subcutaneous and Metastatic Lesions in a Pheochromocytoma Mouse Model after Immunotherapy Using Mannan-BAM, TLR Ligands, and Anti-CD40. Cancers 30 31083581
2019 The Synthetic Phenotype of ΔbamB ΔbamE Double Mutants Results from a Lethal Jamming of the Bam Complex by the Lipoprotein RcsF. mBio 30 31113901
2017 Studying assembly of the BAM complex in native membranes by cellular solid-state NMR spectroscopy. Journal of structural biology 30 29197585
2009 Functional characterization of cohesin SMC3 and separase and their roles in the segregation of large and minichromosomes in Trypanosoma brucei. Molecular microbiology 30 19183276
2022 DNA passes through cohesin's hinge as well as its Smc3-kleisin interface. eLife 29 36094369
2022 Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding. Communications biology 28 35676411
2003 The cohesin SMC3 is a target the for beta-catenin/TCF4 transactivation pathway. The Journal of biological chemistry 28 12651860
2009 Direct inhibition of Pumilo activity by Bam and Bgcn in Drosophila germ line stem cell differentiation. The Journal of biological chemistry 27 20018853
1994 Adrenal secretion of BAM-22P, a potent opioid peptide, is enhanced in rats with acute cholestasis. The American journal of physiology 27 8141292
2022 Stepwise GATA1 and SMC3 mutations alter megakaryocyte differentiation in a Down syndrome leukemia model. The Journal of clinical investigation 26 35587378
2019 Improper Coordination of BamA and BamD Results in Bam Complex Jamming by a Lipoprotein Substrate. mBio 26 31113900
2013 Using 2,6-dichlorobenzamide (BAM) degrading Aminobacter sp. MSH1 in flow through biofilters--initial adhesion and BAM degradation potentials. Applied microbiology and biotechnology 26 23670436
2012 BB0324 and BB0028 are constituents of the Borrelia burgdorferi β-barrel assembly machine (BAM) complex. BMC microbiology 26 22519960
2010 Comparative molecular epidemiology of Leishmania major and Leishmania tropica by PCR-RFLP technique in hyper endemic cities of Isfahan and Bam, Iran. Medical science monitor : international medical journal of experimental and clinical research 26 20980956
2003 A Neurexin-related protein, BAM-2, terminates axonal branches in C. elegans. Science (New York, N.Y.) 26 14551437
1986 Opioid peptides in rat islets of Langerhans. Immunoreactive met- and leu-enkephalins and BAM-22P. Diabetes 26 3510138
2023 ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex. Nucleic acids research 25 37377435
2024 Outer membrane protein assembly mediated by BAM-SurA complexes. Nature communications 24 39218969
2022 Genome-wide identification of BAM (β-amylase) gene family in jujube (Ziziphus jujuba Mill.) and expression in response to abiotic stress. BMC genomics 24 35698031
2021 High-throughput suppressor screen demonstrates that RcsF monitors outer membrane integrity and not Bam complex function. Proceedings of the National Academy of Sciences of the United States of America 24 34349021
2020 The assembly of β-barrel membrane proteins by BAM and SAM. Molecular microbiology 24 33314350
2017 Smc3 Deacetylation by Hos1 Facilitates Efficient Dissolution of Sister Chromatid Cohesion during Early Anaphase. Molecular cell 24 29100057
2013 Imbalance of SMC1 and SMC3 cohesins causes specific and distinct effects. PloS one 24 23776448
2003 Impact of deletions within the Bam HI-L fragment of attenuated Marek's disease virus on vIL-8 expression and the newly identified transcript of open reading frame LORF4. Virus genes 24 12876454
2021 Combining Cell Envelope Stress Reporter Assays in a Screening Approach to Identify BAM Complex Inhibitors. ACS infectious diseases 23 34125508
2018 Smc3 is required for mouse embryonic and adult hematopoiesis. Experimental hematology 23 30553776
1994 Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand. Molecular immunology 23 7514269
2023 Targeting BAM for Novel Therapeutics against Pathogenic Gram-Negative Bacteria. Antibiotics (Basel, Switzerland) 22 37107041
2021 Genome-wide identification of BAM genes in grapevine (Vitis vinifera L.) and ectopic expression of VvBAM1 modulating soluble sugar levels to improve low-temperature tolerance in tomato. BMC plant biology 22 33771117
2021 Bam-readcount - rapid generation of basepair-resolution sequence metrics. ArXiv 22 34341766
2017 The Germline Linker Histone dBigH1 and the Translational Regulator Bam Form a Repressor Loop Essential for Male Germ Stem Cell Differentiation. Cell reports 22 29241545
1999 Complete cDNA cloning, genomic organization, chromosomal assignment, functional characterization of the promoter, and expression of the murine Bamacan gene. The Journal of biological chemistry 22 10358101
1987 Pharmacological properties of a proenkephalin A-derived opioid peptide: BAM 18. European journal of pharmacology 21 3040439
2011 Quantitative analysis of cohesin complex stoichiometry and SMC3 modification-dependent protein interactions. Journal of proteome research 20 21699228
1979 Studies of viable T4 bacteriophage containing cytosine-substituted DNA (T4dC phage). II. Cleavage of T4dC DNA by endonuclease SalI and bam HI. Molecular & general genetics : MGG 20 372740
2021 A ban on BAM: an update on inhibitors of the β-barrel assembly machinery. FEMS microbiology letters 19 34048543

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