Affinage

SPO11

Meiotic recombination protein SPO11 · UniProt Q9Y5K1

Length
396 aa
Mass
44.5 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPO11 is the meiosis-specific catalytic enzyme that initiates homologous recombination by introducing programmed DNA double-strand breaks (DSBs), becoming covalently attached to break ends through a topoisomerase-like transesterase mechanism that links it to DNA via a 5'-phosphotyrosyl bond (PMID:9039264, PMID:39972130). Structurally related to the archaeal topoisomerase VI A subunit (PMID:10545127), SPO11 is monomeric in solution and requires dimerization to reconstitute two hybrid active sites for cleavage; reconstituted with purified mouse protein it cleaves DNA, can reseal nicks, and selects sites according to DNA sequence, bendability and topology (PMID:39972130, PMID:39972129). Its obligate partner TOP6BL forms a 1:1 complex that enhances binding to DNA ends (PMID:39972130), and in budding yeast the catalytic core assembles with Rec102, Rec104 and the scaffold Ski8 into a monomeric complex whose Rec102/Rec104 module resembles the topoisomerase VI B subunit; cryo-EM shows this core gripping the DNA backbone, recessed 3'-OH and 5' overhang to set end-binding specificity (PMID:33398171, PMID:39304764). Cleavage favors bent, topologically stressed DNA and can occur as concerted double DSBs that generate gaps with ~10.5 bp helical periodicity, reflecting fixed orientation of adjacent SPO11 molecules on the DNA helix (PMID:34108687, PMID:34108684). SPO11 acts within an axis-tethering machinery in which Rec114, Mer2 and Mei4 link hotspot sequences to chromosome axis components through Cdk-phosphorylated Mer2 (PMID:21816273), with localization patterned by Rec8 cohesin sites (PMID:19439448). After cleavage, SPO11 is released from break ends as SPO11-oligonucleotide complexes through MRN/Mre11-dependent endonucleolytic processing, promoted by a direct SPO11-Mre11 interaction via SPO11's C-terminus that also recruits Mre11 to chromatin (PMID:19752195, PMID:38407383, PMID:31965061). SPO11-generated DSBs are required for homologous chromosome synapsis and act upstream of ATM kinase, which phosphorylates H2AX and controls break number and processing (PMID:11106738, PMID:15998665, PMID:32051414); SPO11 additionally has a catalysis-independent role in early pre-DSB chromosome pairing (PMID:23318132).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1997 High

    Established that Spo11 is the enzyme that physically makes meiotic DSBs, by showing it is covalently bound to break ends — defining the molecular origin of meiotic recombination initiation.

    Evidence Biochemical purification of covalent protein-DNA complexes from rad50S meiotic yeast

    PMID:9039264

    Open questions at the time
    • Did not resolve the catalytic mechanism or active-site residue
    • Oligomeric state and partner requirements unknown
  2. 1999 High

    Provided a structural template for Spo11 mechanism by solving the archaeal Top6A homolog, revealing a dimeric architecture shared with type II topoisomerases.

    Evidence X-ray crystallography of M. jannaschii Top6A core at 2.0 Å

    PMID:10545127

    Open questions at the time
    • Homology-based inference, not Spo11 structure itself
    • No DNA-bound state
  3. 1999 Medium

    Identified mammalian SPO11 orthologs and their expression pattern, extending the yeast machinery to mouse and human.

    Evidence cDNA cloning, Northern/RT-PCR, FISH mapping

    PMID:10534401

    Open questions at the time
    • No functional assay in mammals
    • Discrepancy between testis-specific and broader expression unresolved
  4. 2000 High

    Demonstrated that mammalian SPO11-mediated DSBs are required for recombination initiation and chromosome synapsis, with breaks acting upstream of pairing in mammals.

    Evidence Spo11-/- mouse knockouts, Rad51/Dmc1 focus immunofluorescence, cisplatin DSB rescue

    PMID:11106738 PMID:11106739

    Open questions at the time
    • Did not separate catalytic from structural roles
    • Mechanism of synapsis dependence on DSBs not defined
  5. 2002 Medium

    Showed Spo11 functions within a multiprotein DSB complex by identifying Rec102 as a physical and genetic partner.

    Evidence Co-IP from meiotic yeast extracts, genetic synthetic interaction, IF on spreads

    PMID:11805049

    Open questions at the time
    • Stoichiometry and architecture of the complex undefined
    • Single lab
  6. 2004 High

    Defined Ski8 as a direct Spo11 partner and scaffold that drives nuclear relocalization and recruitment of other DSB factors.

    Evidence Two-hybrid, chromatin association, fractionation, genetic analysis

    PMID:14992724

    Open questions at the time
    • Molecular basis of scaffolding not structurally resolved
  7. 2004 Medium

    Showed purified fission yeast Rec12/Spo11 is monomeric, implying cofactors are needed to assemble an active dimer.

    Evidence Recombinant purification and gel filtration

    PMID:15477092

    Open questions at the time
    • Single method for oligomeric state
    • No catalytic activity tested
  8. 2005 High

    Mapped how Spo11 engages hotspots transiently and noncovalently, requiring accessory proteins and a catalytic tyrosine (Y135) to form the cleavage intermediate.

    Evidence ChIP in multiple mutant backgrounds, active-site mutant analysis

    PMID:15655113

    Open questions at the time
    • How accessory proteins establish the association mechanistically not resolved
  9. 2005 High

    Placed SPO11-induced DSBs upstream of ATM in the meiotic checkpoint, with ATM mediating chromatin-wide H2AX phosphorylation.

    Evidence Compound Spo11-/-/Atm-/- mouse genetics, γH2AX immunofluorescence

    PMID:15998665

    Open questions at the time
    • Direct biochemical link between SPO11 breaks and ATM activation not shown
  10. 2005 Medium

    Confirmed a conserved active-site residue (Rec12 Gly-202) essential for catalysis but not stability, and noted persistence of Spo11 protein after recombination.

    Evidence Site-directed mutagenesis, recombination assays, protein persistence cytology

    PMID:16009511

    Open questions at the time
    • Putative post-recombination function not defined
    • Single lab
  11. 2007 Medium

    Demonstrated Spo11 self-associates at DSB sites at the time of break formation, dependent on accessory proteins and catalytic activity, linking dimerization to cleavage in vivo.

    Evidence Reciprocal co-IP of tagged Spo11, Gal4BD-Spo11 targeting, ChIP

    PMID:17264124

    Open questions at the time
    • Did not reconstitute dimer-dependent cleavage biochemically
    • Single lab
  12. 2009 High

    Defined the removal pathway: Spo11 is excised from DSB ends as a Spo11-oligonucleotide complex by Mre11 endonuclease activity with Ctp1/Sae2 and Rad50.

    Evidence Detection of Spo11/Rec12-oligo complexes, nuclease mutant analysis in fission yeast

    PMID:19752195

    Open questions at the time
    • Direct Spo11-Mre11 interaction not yet shown
    • Nbs1 role left ambiguous
  13. 2009 High

    Mapped genome-wide Spo11 localization and linked it to Rec8 cohesin sites, connecting break distribution to chromosome organization.

    Evidence ChIP-chip with REC8 deletion in budding yeast

    PMID:19439448

    Open questions at the time
    • Causal mechanism of cohesin-directed positioning not resolved
  14. 2009 High

    Showed Spo11 itself contributes intrinsic sequence preference to cleavage-site choice within a defined DSB targeting window.

    Evidence Single-nucleotide DSB mapping of Gal4BD-Spo11, mutagenesis of Spo11 and target DNA

    PMID:19380488

    Open questions at the time
    • Structural basis of sequence preference not yet defined
  15. 2011 High

    Revealed that hotspot sequences are tethered to the chromosome axis by Rec114/Mer2/Mei4 through Cdk-phosphorylated Mer2 prior to DSB formation.

    Evidence ChIP-chip, mutant and Mer2 phosphorylation analysis in yeast

    PMID:21816273

    Open questions at the time
    • Physical coupling of tether to Spo11 catalysis not biochemically reconstituted
  16. 2013 High

    Separated SPO11's two roles, showing early pre-DSB homolog pairing requires SPO11 protein but not its catalytic activity, alongside SUN1.

    Evidence Spo11-/- and catalytic-mutant mice, FISH pairing assays

    PMID:23318132

    Open questions at the time
    • Molecular mechanism of catalysis-independent pairing role unknown
  17. 2017 Medium

    Showed purified C. elegans SPO-11 binds dsDNA but cannot cleave alone, reinforcing the requirement for cofactors.

    Evidence Recombinant purification, DNA binding and cleavage assays under many conditions

    PMID:28539630

    Open questions at the time
    • Negative cleavage result; cofactors enabling activity not identified here
  18. 2020 High

    Demonstrated ATM governs both SPO11 break number and processing, with PRDM9 asymmetry trapping SPO11 on one DSB end as recombination intermediates.

    Evidence END-seq detecting SPO11-bound intermediates in Atm-/- and Dmc1 mutant spermatocytes

    PMID:32051414

    Open questions at the time
    • Mechanism of asymmetric MRE11 blockage by PRDM9 not fully defined
  19. 2020 Medium

    Established NBS1 as essential for resecting SPO11-linked DSBs in mouse meiosis via an MDC1-independent route distinct from somatic cells.

    Evidence Conditional NBS1 germ-cell knockout, resection-marker IF

    PMID:31965061

    Open questions at the time
    • Identity of phosphoproteins recruiting NBS1 unknown
    • Single lab
  20. 2020 Medium

    Identified hnRNPH/Sam68 competition as the regulatory switch controlling SPO11α/β isoform splicing during meiosis.

    Evidence Splicing factor screening, competition binding, RNAPII phosphorylation analysis

    PMID:32303676

    Open questions at the time
    • Functional consequence of isoform ratio not mechanistically tied to DSB output
    • Single lab
  21. 2021 High

    Reconstituted the budding yeast Spo11 core complex, defining its 1:1:1:1 monomeric stoichiometry, topoisomerase-VI-like architecture, and DNA end-capping behavior.

    Evidence Biochemical reconstitution, stoichiometry and DNA binding assays, interface mutagenesis validated in vivo

    PMID:33398171

    Open questions at the time
    • Did not capture catalytically active dimeric state
    • No high-resolution DNA-bound structure
  22. 2021 High

    Showed Spo11 makes concerted double DSBs with ~10.5 bp periodicity, indicating fixed orientation of adjacent enzymes on the helix and generating recombinogenic gaps.

    Evidence Spo11-oligo-seq in yeast and mice, in vitro core-complex DNA binding, progeny sequencing

    PMID:34108684 PMID:34108687

    Open questions at the time
    • How concerted cleavage is physically coordinated between enzymes not structurally resolved
  23. 2021 High

    Implicated topological stress and DNA crossings in Spo11 break formation through gap-fragment periodicity and overlap with topoisomerase II sites.

    Evidence Genome-wide gap-fragment mapping, TopoII site overlap, sequence analysis

    PMID:34108684

    Open questions at the time
    • Direct test of topological stress requirement in vitro not provided here
  24. 2021 Medium

    Uncovered a destructive activity of Spo11, showing ectopic Spo11 with Rec8 can dismantle centromeres and kinetochores in fission yeast and human cells.

    Evidence Spo11 overexpression, kinetochore-marker and bouquet-mutant analysis

    PMID:33658710

    Open questions at the time
    • Physiological relevance to normal meiosis unclear
    • Single lab
  25. 2023 Medium

    Identified FUS/TLS as a SPO11-interacting factor that links the recombination machinery to PRDM9-marked hotspots.

    Evidence Co-IP in vitro and in vivo, IF, ChIP at H3K4me3 hotspots

    PMID:36967403

    Open questions at the time
    • Functional role of FUS/TLS in DSB formation not established
    • Single lab
  26. 2024 High

    Resolved the DNA-bound Spo11 core complex by cryo-EM, defining how it grips recessed 3'-OH and 5' overhang to specify end-binding.

    Evidence Cryo-EM up to 3.3 Å with in vivo mutagenesis validation in yeast (peer-reviewed; preprint 37961437)

    PMID:37961437 PMID:39304764

    Open questions at the time
    • Structure represents post-cleavage end-binding rather than active cleavage state
  27. 2024 High

    Demonstrated a direct Spo11-Mre11 interaction via Spo11's C-terminus that modulates Mre11 activities and recruits it to chromatin independently of DSBs.

    Evidence In vitro interaction and nuclease assays, calibrated Mre11 ChIP, mutant analysis in yeast

    PMID:38407383

    Open questions at the time
    • Structural basis of the Spo11-Mre11 interface not determined
  28. 2025 High

    Achieved full in vitro reconstitution of mammalian SPO11 catalysis, proving SPO11 alone cleaves DNA, requires dimerization for two hybrid active sites, can reseal nicks, and forms a 1:1 complex with TOP6BL that enhances end binding.

    Evidence In vitro reconstitution with recombinant mouse SPO11 and SPO11-TOP6BL, active-site and dimerization mutagenesis, AlphaFold 3 modeling

    PMID:39972129 PMID:39972130

    Open questions at the time
    • High-resolution experimental structure of the active dimer not solved
    • How dimerization is regulated in vivo not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How accessory proteins and chromosome-axis context trigger SPO11 dimerization and concerted cleavage at the right time and place in vivo remains unresolved.
  • No structure of the catalytically active SPO11 dimer on DNA
  • Spatiotemporal control of dimerization and double-DSB coordination undefined
  • Catalysis-independent pairing mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0016787 hydrolase activity 3 GO:0140097 catalytic activity, acting on DNA 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 3
Partners
FUSMRE11REC102REC104REC114SKI8TOP6BL
Complex memberships
SPO11 core complex (Spo11-Rec102-Rec104-Ski8)SPO11-TOP6BL complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Spo11 is the catalytic subunit responsible for meiotic DNA double-strand break (DSB) formation; it becomes covalently attached to DSB ends via a topoisomerase-like transesterase mechanism, demonstrated by purification of protein-DNA complexes from rad50S mutants and identification of the covalently bound protein as Spo11. Biochemical purification of protein-DNA complexes from meiotic yeast cells; protein identification; covalent protein-DNA linkage demonstrated Cell High 9039264
1999 The crystal structure of the archaeal topoisomerase VI A subunit (Top6A), the structural homolog of Spo11, was solved at 2.0 Å resolution. The core structure is a dimer with a deep groove spanning both protomers, containing domain pairs shared with type IA and classic type II topoisomerases, providing a structural template for probing Spo11 function. X-ray crystallography at 2.0 Å resolution of M. jannaschii Top6A DNA-binding core The EMBO journal High 10545127
1999 Mouse and human SPO11 are orthologs of yeast Spo11 with ~25% identity to other family members; mouse Spo11 localizes to chromosome 2H4 and human SPO11 to chromosome 20q13.2-q13.3; expression is testis-specific by Northern blot but broader by RT-PCR. cDNA cloning; Northern blot; RT-PCR; chromosomal localization by FISH Genomics Medium 10534401
2000 Mouse Spo11 is required for meiotic DSB formation (evidenced by absence of Rad51/Dmc1 foci in Spo11-/- spermatocytes) and for chromosome synapsis; Spo11 protein localizes to discrete foci during leptotene and to synapsed chromosomes; cisplatin-induced DSBs restored Rad51/Dmc1 foci and promoted synapsis in Spo11-/- cells. Gene knockout (Spo11-/- mice); immunofluorescence on meiotic chromosome spreads; cisplatin rescue experiment Molecular cell High 11106738
2000 Disruption of mouse Spo11 abolishes Dmc1/Rad51 focus formation, causes homologous chromosome synapsis defects in spermatocytes, and results in sexually dimorphic checkpoint responses; recombination initiation precedes and is required for normal synapsis in mammals. Gene knockout (Spo11-/- mice); immunofluorescence for Dmc1/Rad51 foci; cytological analysis of meiotic spreads Molecular cell High 11106739
2002 Spo11 physically interacts with Rec102 in vivo (co-immunoprecipitation from meiotic cell extracts); tagged Rec102 localizes to the nucleus and to chromatin on spread meiotic chromosomes; genetic synthetic cold-sensitive interaction between tagged SPO11 and tagged REC102 severely reduces DSB formation, demonstrating they function in a common complex. Co-immunoprecipitation from meiotic yeast extracts; genetic epistasis (synthetic phenotype); immunofluorescence on chromosome spreads Genetics Medium 11805049
2004 Ski8 is a direct physical partner of Spo11 required for meiotic DSB formation; Ski8 relocalizes from cytoplasm to nucleus specifically during meiosis, and this relocalization requires its interaction with Spo11; Ski8 works with Spo11 to recruit other DSB proteins to meiotic chromosomes, functioning as a scaffold for multiprotein complex assembly. Two-hybrid analysis; chromatin association assays; genetic analysis; nuclear/cytoplasmic fractionation during meiosis Molecular cell High 14992724
2005 Spo11 transiently and noncovalently associates with meiotic recombination hotspots; establishment of this association requires Rec102, Rec104, and Rec114; timely removal of Spo11 from chromatin depends on Mei4 and Ndt80; Red1 locally restricts Spo11's interaction to the core hotspot region. In rad50S and com1Δ/sae2Δ mutants, Spo11 forms a reversible cleavage intermediate detectable without crosslinking, requiring Spo11's catalytic residue Y135. Chromatin immunoprecipitation (ChIP); mutant analysis; chromosome spreads with immunofluorescence Genes & development High 15655113
2005 SPO11 is required for H2AX phosphorylation (sex-body formation) in mouse spermatocytes; Spo11 heterozygosity rescues the prophase-I arrest of Atm-/- spermatocytes, placing SPO11-induced DSBs upstream of ATM in the meiotic checkpoint pathway; ATM mediates chromatin-wide H2AX phosphorylation in leptotene in response to DSBs; ATR, not ATM, is the kinase responsible for H2AX phosphorylation in the sex body. Mouse genetic crosses (Spo11-/-, Atm-/-, compound mutants); immunofluorescence for γ-H2AX; chromosome spread analysis Journal of cell science High 15998665
2007 Spo11 self-associates in vivo during meiosis at the time of DSB formation; Gal4BD-Spo11 fusion can recruit Spo11-3FLAG to GAL2 locus forming a heterocomplex, but the nuclease-deficient Gal4BD-spo11Y135F does not produce breaks; Spo11 self-interaction at DSB sites depends on Rec102, Rec104, and Rec114; in cold chromosomal domains, Spo11 binds but does not self-associate or form DSBs. Co-immunoprecipitation of differentially tagged Spo11 proteins; Gal4BD-Spo11 targeting; ChIP; genetic analysis of self-interaction in hot vs. cold domains Nucleic acids research Medium 17264124
2009 Spo11 is removed from meiotic DSB ends by endonucleolytic cleavage, releasing Spo11 covalently attached to a short oligonucleotide (Spo11-oligonucleotide complex); in fission yeast, a single size class of Rec12 (Spo11)-oligonucleotide complexes is generated, requiring the Rad32 (Mre11) nuclease domain, Ctp1 (Sae2 homolog), and Rad50; Nbs1 is not strictly required. Detection and purification of Spo11/Rec12-oligonucleotide complexes from meiotic yeast; nuclease mutant analysis Molecular and cellular biology High 19752195
2009 Spo11 genome-wide localization in budding yeast shows it dynamically localizes first around centromeres then to arm regions during premeiotic S phase; a substantial proportion of Spo11 binds to Rec8 cohesin binding sites; deletion of REC8 influences Spo11 localization to centromeres and chromosomal arm regions, correlating with loss of DSBs in specific regions. ChIP-chip (chromatin immunoprecipitation with tiling arrays) in budding yeast; REC8 deletion analysis Molecular biology of the cell High 19439448
2009 Locally at recombination hotspots, Gal4BD-Spo11 introduces DSBs at discrete sites approximately 20 nucleotides from Gal4 binding sites (a 'DSB targeting window'); mutations in the Spo11 moiety affect DSB distribution within this window; mutations at the Spo11 cleavage site affect DSB position, demonstrating that Spo11 itself has sequence preference contributing to cleavage site choice. Single-nucleotide resolution DSB mapping of targeted Gal4BD-Spo11 cleavage; site-directed mutagenesis of Spo11 and target DNA Molecular and cellular biology High 19380488
2011 Spo11-accessory proteins Rec114, Mer2, and Mei4 stably interact with chromosome axis sequences (Red1/Hop1 axis components) through phosphorylation of Mer2 by S-phase Cdk; this axis tethering is modulated by cohesin; loss of Rec114, Mer2, Mei4 binding correlates with loss of DSBs, suggesting hotspot sequences are tethered to axis sites by the DSB machinery prior to DSB formation. ChIP-chip in yeast; mutant analysis; phosphorylation analysis of Mer2 Cell High 21816273
2013 In mouse, a significant level of homologous chromosome pairing precedes SPO11-mediated DSBs; this early pre-DSB pairing still requires SPO11 protein but is independent of its DSB-inducing catalytic activity; SUN1 is also required for this pre-DSB pairing. Spo11-/- mice and Spo11 catalytic mutant analysis; FISH-based chromosome pairing assays; SUN1 mutant analysis Developmental cell High 23318132
2020 SPO11-bound recombination intermediates (SPO11-RI) form at all hotspots because PRDM9 asymmetrically blocks MRE11 from releasing SPO11 from one DSB end; in Atm-/- spermatocytes, trapped SPO11 cleavage complexes accumulate due to defective MRE11 initiation of resection; ATM governs both SPO11 breakage number and SPO11 processing. END-seq on mouse spermatocytes; enzymatic modifications to detect SPO11-bound intermediates; Atm-/- mutant analysis; DMC1 mutant analysis Nature communications High 32051414
2020 NBS1 (component of MRN complex) is essential for repairing SPO11-linked DSBs in male mouse meiosis; NBS1 loss causes dramatic reduction of DNA end resection and defective HR; unlike in somatic cells, NBS1 recruitment to SPO11-linked DSB sites is MDC1-independent but requires other phosphorylated proteins. Conditional NBS1 knockout in male germ cells; immunofluorescence for resection markers; chromosome spread analysis Cell death and differentiation Medium 31965061
2021 Spo11 forms concerted (double) DSBs separated by 33 to >100 bp; the lengths of double cuts vary with a periodicity of ~10.5 bp (conserved in yeast and mice), indicating orientation of adjacent Spo11 molecules is fixed relative to the DNA helix; the Spo11 core complex binds DNA in vitro with properties consistent with this model; these double cuts generate DNA gaps that can initiate recombination independently of Msh2-dependent heteroduplex repair. Spo11-oligonucleotide sequencing (Spo11-oligo-seq) in yeast and mice; in vitro DNA-binding assays of Spo11 core complex; deep sequencing of meiotic progeny Nature High 34108687
2021 Spo11 generates DNA gaps (34 to several hundred bp) through coordinated pairs of DSBs (double DSBs); fragment lengths have periodicity of ~(10.4n + 3) bp indicating Spo11 favors cleavage on the same face of underwound DNA; double DSB signals overlap with topoisomerase II binding sites, implicating topological stress and DNA crossings in break formation; Spo11 prefers sequences with similarity to a DNA-bending motif. Isolation and genome-wide mapping of gap fragments with single base-pair precision; overlap with TopoII binding sites; sequence analysis of cleavage preferences Nature High 34108684
2021 Spo11 core complex (with Rec102, Rec104, Ski8) is monomeric with 1:1:1:1 stoichiometry; Rec102 and Rec104 jointly resemble the B subunit of archaeal topoisomerase VI, with Rec104 occupying a position similar to the Top6B GHKL-type ATPase domain; reconstituted complex shows topoisomerase-like preferences for duplex-duplex junctions and bent DNA; Spo11 binds DNA ends with high affinity (mimicking cleavage products), suggesting a mechanism to cap DSB ends; mutations reducing DNA binding in vitro attenuate DSB formation and alter DSB landscape in vivo. Biochemical reconstitution; purification of Spo11 complex; stoichiometry analysis; in vitro DNA binding assays; active-site/interface mutagenesis correlated with in vivo DSB formation Nature structural & molecular biology High 33398171
2021 Spo11 and meiotic cohesin Rec8 can dismantle centromeres; specific nucleosome remodeling factors mediate centromere dismantlement by Spo11; ectopic expression of Spo11 in proliferating cells leads to loss of mitotic kinetochores in fission yeast and human cells. Overexpression of Spo11 in fission yeast and human cells; analysis of centromere/kinetochore markers; genetic analysis with bouquet mutants Nature Medium 33658710
2024 Cryo-EM structures at up to 3.3-Å resolution of DNA-bound Spo11 core complex (with Rec102, Rec104, Ski8) reveal monomeric complexes making extensive contacts with DNA backbone and recessed 3'-OH and first 5' overhanging nucleotide, establishing molecular determinants of DNA end-binding specificity; metal ions play a role in DNA binding; unexpected structural variation exists in Top6BL homologs; functional data in yeast supports structural conclusions. Cryo-electron microscopy (up to 3.3 Å resolution); in vivo functional validation by mutagenesis in yeast Nature structural & molecular biology High 39304764
2024 Spo11 physically interacts with Mre11 via Spo11's far C-terminal region; this interaction modulates Mre11's DNA binding, bridging, and nuclease activities; Spo11 promotes Mre11 recruitment to meiotic chromatin independently of DSB formation; a Spo11 mutant deficient in Mre11 interaction severely reduces Mre11 chromatin association and impedes DSB formation. Purification of Spo11 fragments; in vitro protein interaction and nuclease assays; calibrated ChIP for Mre11 in yeast; mutant analysis Nucleic acids research High 38407383
2025 Mouse SPO11 alone (without partners) catalyzes DSB formation in vitro, remaining covalently attached to 5' broken strands; SPO11 is monomeric in solution and dimerization is required for cleavage through reconstitution of two hybrid active sites; SPO11 can reseal single-strand DNA nicks; SPO11 and TOP6BL form a 1:1 complex that catalyzes DNA cleavage with similar activity to SPO11 alone but binds DNA ends with higher affinity; target site selection is influenced by DNA sequence, bendability, and topology. In vitro reconstitution with purified recombinant mouse SPO11; biochemical DSB assay; covalent 5'-attachment assay; SPO11-TOP6BL complex formation and cleavage; dimerization analysis Nature High 39972130
2025 Mouse SPO11-TOP6BL complexes are monomeric (1:1) in solution but dimeric (2:2) assemblies cleave DNA via covalent 5' attachments requiring SPO11 active-site residues, divalent metal ions, and SPO11 dimerization; SPO11 can reseal nicked DNA; cleavage is inefficient when SPO11 is trapped in monomeric binding states; artificial dimerization improves cleavage; AlphaFold 3 structural modeling suggests DNA bending prior to cleavage. In vitro reconstitution with purified recombinant mouse SPO11-TOP6BL; active-site mutagenesis; dimerization analysis; AlphaFold 3 modeling; artificial dimerization experiments Nature High 39972129
2020 hnRNPH is a key regulator of SPO11α splicing in mouse spermatocytes by competing with Sam68 (a positive regulator of SPO11β splicing) for binding near exon 2 of Spo11 pre-mRNA; modulation of RNA polymerase II phosphorylation and processivity near exon 2 favors hnRNPH recruitment, enabling combinatorial control of the SPO11α/β splicing switch during meiosis. Splicing factor screening; RNA binding assays; RNAPII phosphorylation analysis; competition binding between hnRNPH and Sam68 on Spo11 pre-mRNA; in vitro and in vivo splicing assays Cell death & disease Medium 32303676
2023 FUS/TLS physically interacts with SPO11 (both in vitro and in vivo by co-immunoprecipitation) and with PRDM9 and REC114; FUS/TLS colocalizes with PRDM9 on meiotic chromosome axes and is localized at H3K4me3-marked recombination hotspots by ChIP. Co-immunoprecipitation (in vitro and in vivo); immunofluorescence on meiotic chromosomes; chromatin immunoprecipitation (ChIP) Cellular and molecular life sciences Medium 36967403
2004 Fission yeast Rec12 (Spo11) protein was purified in refolded soluble form; gel filtration demonstrated it exists as a monomer in solution, suggesting additional proteins may be required to assemble biologically active dimers. Recombinant protein expression and purification; refolding optimization; gel filtration chromatography Protein expression and purification Medium 15477092
2017 C. elegans SPO-11 is monomeric, binds double-stranded DNA preferentially, but does not exhibit DNA cleavage activity under a wide range of reaction conditions in vitro, suggesting co-factors are required for DSB induction activity. Recombinant protein expression and purification; biochemical DNA binding assays; in vitro cleavage assays under multiple conditions Scientific reports Medium 28539630
2005 Glycine-202 of Rec12 (Spo11), conserved in all Rec12/Spo11/Top6A family members and mapping to the base of the DNA binding pocket in the archaeal crystal structure, is essential for catalytic activity but not protein stability; rec12-G202E mutants lack all crossover and non-crossover recombination; bulk Rec12 protein persists until anaphase I, with a portion persisting until anaphase II, suggesting post-recombination functions. Site-directed mutagenesis; genetic recombination assays; protein stability analysis; cytological timing of Rec12 protein persistence Gene Medium 16009511
2023 Cryo-EM structures of DNA-bound Spo11 core complex (Spo11-Rec102-Rec104-Ski8) at up to 3.3-Å resolution show monomeric complexes making extensive contacts with DNA backbone and with recessed 3'-OH and first 5' overhanging nucleotide; structural data inform DNA cleavage preferences in vivo; metal ions contribute to DNA binding; structural variation exists in Top6BL homologs. Cryo-electron microscopy; functional mutagenesis in yeast bioRxivpreprint High 37961437

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 1457 9039264
2000 The mouse Spo11 gene is required for meiotic chromosome synapsis. Molecular cell 645 11106738
2000 Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Molecular cell 579 11106739
2011 Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination. Cell 302 21816273
2008 Spo11 and the Formation of DNA Double-Strand Breaks in Meiosis. Genome dynamics and stability 257 21927624
1998 mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved. Genes & development 231 9744869
1985 The role of the SPO11 gene in meiotic recombination in yeast. Genetics 227 3891509
2005 SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes. Journal of cell science 162 15998665
1999 Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo11. The EMBO journal 150 10545127
2004 Antiviral protein Ski8 is a direct partner of Spo11 in meiotic DNA break formation, independent of its cytoplasmic role in RNA metabolism. Molecular cell 141 14992724
1999 Cloning, characterization, and localization of mouse and human SPO11. Genomics 124 10534401
2013 Homologous pairing preceding SPO11-mediated double-strand breaks in mice. Developmental cell 122 23318132
2000 Multiple roles of Spo11 in meiotic chromosome behavior. The EMBO journal 110 10835371
2020 ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis. Nature communications 96 32051414
2009 Rec8 guides canonical Spo11 distribution along yeast meiotic chromosomes. Molecular biology of the cell 92 19439448
2007 Protist homologs of the meiotic Spo11 gene and topoisomerase VI reveal an evolutionary history of gene duplication and lineage-specific loss. Molecular biology and evolution 90 17921483
2001 Molecular characterization of homologues of both subunits A (SPO11) and B of the archaebacterial topoisomerase 6 in plants. Gene 86 11410368
2009 Meiotic DNA double-strand break repair requires two nucleases, MRN and Ctp1, to produce a single size class of Rec12 (Spo11)-oligonucleotide complexes. Molecular and cellular biology 83 19752195
2005 The control of Spo11's interaction with meiotic recombination hotspots. Genes & development 83 15655113
2010 Evolutionary conservation of meiotic DSB proteins: more than just Spo11. Genes & development 73 20551169
2013 SPO11-independent DNA repair foci and their role in meiotic silencing. PLoS genetics 69 23754961
2021 Concerted cutting by Spo11 illuminates meiotic DNA break mechanics. Nature 68 34108687
2021 Structural and functional characterization of the Spo11 core complex. Nature structural & molecular biology 66 33398171
2007 Characterization of Spo11-dependent and independent phospho-H2AX foci during meiotic prophase I in the male mouse. Journal of cell science 64 17456548
2002 Functional interactions between SPO11 and REC102 during initiation of meiotic recombination in Saccharomyces cerevisiae. Genetics 56 11805049
2002 Distinct functions of S. pombe Rec12 (Spo11) protein and Rec12-dependent crossover recombination (chiasmata) in meiosis I; and a requirement for Rec12 in meiosis II. Cell & chromosome 56 12437782
2002 Wild-type levels of Spo11-induced DSBs are required for normal single-strand resection during meiosis. Molecular cell 53 11983174
2000 Replication-dependent early meiotic requirement for Spo11 and Rad50. Proceedings of the National Academy of Sciences of the United States of America 52 10973500
2021 Spo11 generates gaps through concerted cuts at sites of topological stress. Nature 49 34108684
2007 Meiotic association between Spo11 regulated by Rec102, Rec104 and Rec114. Nucleic acids research 48 17264124
2000 HO endonuclease-induced recombination in yeast meiosis resembles Spo11-induced events. Proceedings of the National Academy of Sciences of the United States of America 44 11121053
2015 Identification of the meiotic toolkit in diatoms and exploration of meiosis-specific SPO11 and RAD51 homologs in the sexual species Pseudo-nitzschia multistriata and Seminavis robusta. BMC genomics 41 26572248
2017 Programming sites of meiotic crossovers using Spo11 fusion proteins. Nucleic acids research 39 28977556
2020 NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis. Cell death and differentiation 36 31965061
2011 OsSpo11-4, a rice homologue of the archaeal TopVIA protein, mediates double-strand DNA cleavage and interacts with OsTopVIB. PloS one 36 21637817
2017 Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11. eLife 35 28621664
2018 Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11-mutant mouse meiocytes, and is altered in the absence of HORMAD1. DNA repair 31 29414051
2013 High throughput sequencing reveals alterations in the recombination signatures with diminishing Spo11 activity. PLoS genetics 31 24204324
2020 Dynamic localization of SPO11-1 and conformational changes of meiotic axial elements during recombination initiation of maize meiosis. PLoS genetics 29 32310948
2016 Atypical ploidy cycles, Spo11, and the evolution of meiosis. Seminars in cell & developmental biology 28 26811992
2020 Assessment of the roles of SPO11-2 and SPO11-4 in meiosis in rice using CRISPR/Cas9 mutagenesis. Journal of experimental botany 26 32842152
2008 Sites of strong Rec12/Spo11 binding in the fission yeast genome are associated with meiotic recombination and with centromeres. Chromosoma 26 18449558
2004 Meiotic chromosome synapsis in yeast can occur without spo11-induced DNA double-strand breaks. Genetics 25 15514052
2014 The splicing fate of plant SPO11 genes. Frontiers in plant science 24 25018755
2007 Targeted induction of meiotic double-strand breaks reveals chromosomal domain-dependent regulation of Spo11 and interactions among potential sites of meiotic recombination. Nucleic acids research 24 18096626
2017 Tex19.1 promotes Spo11-dependent meiotic recombination in mouse spermatocytes. PLoS genetics 23 28708824
2009 Locally, meiotic double-strand breaks targeted by Gal4BD-Spo11 occur at discrete sites with a sequence preference. Molecular and cellular biology 23 19380488
2009 End-labeling and analysis of Spo11-oligonucleotide complexes in Saccharomyces cerevisiae. Methods in molecular biology (Clifton, N.J.) 23 19799183
2002 Most meiotic CAG repeat tract-length alterations in yeast are SPO11 dependent. Molecular genetics and genomics : MGG 23 11919716
2006 Chromosome pairing and meiotic recombination in Neurospora crassa spo11 mutants. Current genetics 22 16758206
2005 Activation of an alternative, rec12 (spo11)-independent pathway of fission yeast meiotic recombination in the absence of a DNA flap endonuclease. Genetics 22 16118186
2000 Identification and characterization of an SPO11 homolog in the mouse. Chromosoma 22 10855504
2025 SPO11 dimers are sufficient to catalyse DNA double-strand breaks in vitro. Nature 21 39972130
2021 Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8. Nature 21 33658710
2025 Reconstitution of SPO11-dependent double-strand break formation. Nature 20 39972129
2020 Combinatorial control of Spo11 alternative splicing by modulation of RNA polymerase II dynamics and splicing factor recruitment during meiosis. Cell death & disease 18 32303676
2011 An association study of SPO11 gene single nucleotide polymorphisms with idiopathic male infertility in Chinese Han population. Journal of assisted reproduction and genetics 18 21556891
2010 Targeted JAM-C deletion in germ cells by Spo11-controlled Cre recombinase. Journal of cell science 18 21147852
2002 Differential association of SMC1alpha and SMC3 proteins with meiotic chromosomes in wild-type and SPO11-deficient male mice. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 18 12498344
2022 Identification, characterization, and rescue of CRISPR/Cas9 generated wheat SPO11-1 mutants. Plant biotechnology journal 17 36373224
2015 A surge of late-occurring meiotic double-strand breaks rescues synapsis abnormalities in spermatocytes of mice with hypomorphic expression of SPO11. Chromosoma 17 26440409
2012 The double-stranded break-forming activity of plant SPO11s and a novel rice SPO11 revealed by a Drosophila bioassay. BMC molecular biology 17 22248237
2010 Mre11 and Exo1 contribute to the initiation and processivity of resection at meiotic double-strand breaks made independently of Spo11. DNA repair 15 21146476
2004 [SPO11: an activity that promotes DNA breaks required for meiosis]. Medecine sciences : M/S 15 14997442
2023 Conserved meiotic mechanisms in the cnidarian Clytia hemisphaerica revealed by Spo11 knockout. Science advances 14 36706182
2002 Mice deficient for the type II topoisomerase-like DNA transesterase Spo11 show normal immunoglobulin somatic hypermutation and class switching. European journal of immunology 14 11807770
2024 Cryo-EM structures of the Spo11 core complex bound to DNA. Nature structural & molecular biology 13 39304764
2013 Suppression of genetic recombination in the pseudoautosomal region and at subtelomeres in mice with a hypomorphic Spo11 allele. BMC genomics 13 23870400
2013 A mutation in the FHA domain of Coprinus cinereus Nbs1 Leads to Spo11-independent meiotic recombination and chromosome segregation. G3 (Bethesda, Md.) 13 24062528
2019 A segregating human allele of SPO11 modeled in mice disrupts timing and amounts of meiotic recombination, causing oligospermia and a decreased ovarian reserve†. Biology of reproduction 12 31074776
2017 Functional characterization of the meiosis-specific DNA double-strand break inducing factor SPO-11 from C. elegans. Scientific reports 12 28539630
2017 An in vivo genetic screen in Drosophila identifies the orthologue of human cancer/testis gene SPO11 among a network of targets to inhibit lethal(3)malignant brain tumour growth. Open biology 12 28855394
2015 SPO11-C631T Gene Polymorphism: Association With Male Infertility and an in Silico-Analysis. Journal of family & reproductive health 12 27047561
2014 Study of single nucleotide polymorphism (rs28368082) in SPO11 gene and its association with male infertility. Journal of assisted reproduction and genetics 12 25005169
2004 Purification, folding, and characterization of Rec12 (Spo11) meiotic recombinase of fission yeast. Protein expression and purification 12 15477092
2017 The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis. Renal failure 11 28050928
2017 Sequencing Spo11 Oligonucleotides for Mapping Meiotic DNA Double-Strand Breaks in Yeast. Methods in molecular biology (Clifton, N.J.) 11 28349390
2018 The cotton endocycle-involved protein SPO11-3 functions in salt stress via integrating leaf stomatal response, ROS scavenging and root growth. Physiologia plantarum 10 30426499
2006 Both conserved and non-conserved regions of Spo11 are essential for meiotic recombination initiation in yeast. Molecular genetics and genomics : MGG 10 16816949
2024 Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity. Nucleic acids research 9 38407383
2021 Rad9, a 53BP1 Ortholog of Budding Yeast, Is Insensitive to Spo11-Induced Double-Strand Breaks During Meiosis. Frontiers in cell and developmental biology 9 33842461
2018 Spo11-Independent Meiosis in Social Amoebae. Annual review of microbiology 9 29924686
2005 A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination. Gene 9 16009511
2020 Long-term exposure to formaldehyde induced down-regulation of SPO11 in rats. Inhalation toxicology 8 33322957
2023 Plasmodium Topoisomerase VIB and Spo11 Constitute Functional Type IIB Topoisomerase in Malaria Parasite: Its Possible Role in Mitochondrial DNA Segregation. Microbiology spectrum 7 37212694
2009 Detection of SPO11-oligonucleotide complexes from mouse testes. Methods in molecular biology (Clifton, N.J.) 7 19799184
2024 Phylogenetic distribution of DNA topoisomerase VI and its distinction from SPO11. NAR genomics and bioinformatics 6 39108638
2023 The proper interplay between the expression of Spo11 splice isoforms and the structure of the pseudoautosomal region promotes XY chromosomes recombination. Cellular and molecular life sciences : CMLS 6 37682311
2022 Early developmental, meiosis-specific proteins - Spo11, Msh4-1, and Msh5 - Affect subsequent genome reorganization in Paramecium tetraurelia. Biochimica et biophysica acta. Molecular cell research 6 35181406
2013 Residual recombination in Neurospora crassa spo11 deletion homozygotes occurs during meiosis. Molecular genetics and genomics : MGG 6 23801409
2023 The RNA-binding protein FUS/TLS interacts with SPO11 and PRDM9 and localize at meiotic recombination hotspots. Cellular and molecular life sciences : CMLS 5 36967403
2000 Mouse homolog of Saccharomyces cerevisiae spo11 is induced in normal mu(+)B-cells by stimuli that cause germline C(H) transcription and subsequent class switch recombination. Cellular immunology 5 10873300
2023 Cryo-EM structure of the Spo11 core complex bound to DNA. bioRxiv : the preprint server for biology 4 37961437
2020 Sexual reproduction potential implied by functional analysis of SPO11 in Phaeodactylum tricornutum. Gene 4 32622990
2015 [Association of SPO11 and GST gene polymorphisms with idiopathic male infertility in ethnic Han Chinese]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 4 26663067
2011 Detection of covalent DNA-bound Spo11 and topoisomerase complexes. Methods in molecular biology (Clifton, N.J.) 4 21660689
2023 Chromosome-dependent aneuploid formation in Spo11-less meiosis. Genes to cells : devoted to molecular & cellular mechanisms 3 36530025
2020 Cloning of the SPO11 gene that complements a meiotic recombination defect in sake yeast. Journal of bioscience and bioengineering 3 32646632
2013 The hidden talents of SPO11. Developmental cell 3 23369711
2001 Class switch recombination signals induce lymphocyte-derived Spo11 expression and Spo11 antisense oligonucleotide inhibits class switching. Cellular immunology 3 11591116

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