Affinage

SPO11

Meiotic recombination protein SPO11 · UniProt Q9Y5K1

Length
396 aa
Mass
44.5 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPO11 is a conserved topoisomerase II-related transesterase that initiates meiotic recombination by catalyzing programmed DNA double-strand breaks through covalent 5′-phosphotyrosyl linkage to break ends (PMID:9039264, PMID:39972129). SPO11 functions as a monomer in solution but requires dimerization to constitute two hybrid active sites for DNA cleavage; it forms a core complex with TOP6BL (or yeast Rec102–Rec104) and Ski8 in a 1:1:1:1 stoichiometry, where Rec102–Rec104 jointly mimic the Top6B subunit, and the complex preferentially binds duplex–duplex junctions, bent DNA, and DNA ends (PMID:33398171, PMID:39304764, PMID:39972130). SPO11 generates concerted double DSBs with ~10.5-bp periodicity reflecting cleavage on the same helical face of underwound DNA, and is subsequently released from break ends as a covalent SPO11-oligonucleotide complex by MRE11/Rad50-Ctp1(Sae2) endonucleolytic processing, which is locally regulated by PRDM9 and ATM (PMID:34108687, PMID:19752195, PMID:32051414). Beyond its catalytic role, SPO11 has DSB-independent functions in pre-DSB homolog pairing and centromere remodeling, and its loss in mice abolishes meiotic DSB formation and homologous chromosome synapsis (PMID:23318132, PMID:33658710, PMID:11106738).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    The identity of the meiotic DSB catalyst was unknown; biochemical purification of covalent protein-DNA complexes from yeast meiotic cells revealed Spo11 as the transesterase that becomes covalently attached to 5′ DSB ends, establishing the catalytic mechanism of meiotic recombination initiation.

    Evidence Biochemical purification and identification of Spo11-DNA covalent complexes from S. cerevisiae meiotic cells

    PMID:9039264

    Open questions at the time
    • No in vitro reconstitution of cleavage activity at this point
    • Structural basis of catalysis unknown
    • Identity of required cofactors unknown
  2. 1999 High

    The structural basis for Spo11's topoisomerase-like mechanism was unclear; the crystal structure of the archaeal homolog Top6A revealed a dimeric architecture with a DNA-binding groove shared between protomers, providing the first structural template for understanding Spo11 cleavage geometry.

    Evidence X-ray crystallography of Methanococcus jannaschii Top6A at 2.0 Å resolution

    PMID:10545127

    Open questions at the time
    • Structure of eukaryotic Spo11 itself unresolved
    • No DNA-bound structure available
    • Mechanism of partner recruitment unknown
  3. 2000 High

    Whether Spo11's role was conserved in mammals and whether DSBs were the trigger for homolog synapsis were open questions; mouse Spo11 knockout abolished Rad51/Dmc1 foci and chromosome synapsis, and cisplatin-induced DSBs restored both, establishing that Spo11-dependent DSBs are required for and precede synapsis in mammals.

    Evidence Mouse Spo11 gene disruption, immunofluorescence for recombination foci, cisplatin rescue experiment

    PMID:11106738 PMID:11106739

    Open questions at the time
    • Catalytic-dead mutant not yet tested in mammals
    • DSB-independent roles of Spo11 not addressed
    • Sexually dimorphic checkpoint responses not mechanistically explained
  4. 2002 High

    The composition of the Spo11 DSB-forming complex was poorly defined; identification of Rec102 as a direct Spo11-interacting partner required for Spo11's chromatin association, and of Ski8 as a meiosis-specific nuclear scaffold for the DSB machinery, established the first components of the Spo11 core complex.

    Evidence Co-immunoprecipitation from meiotic extracts, two-hybrid analysis, chromosome spread immunofluorescence, genetic epistasis

    PMID:11805049 PMID:14992724

    Open questions at the time
    • Stoichiometry of the complex unknown
    • Structural relationship between Rec102/Rec104 and Top6B not yet recognized
    • In vitro reconstitution lacking
  5. 2005 High

    How Spo11 engages recombination hotspots and whether its binding requires accessory factors was unknown; ChIP showed transient Spo11 association at hotspots dependent on Rec102/Rec104/Rec114, with a reversible cleavage intermediate detectable only when Spo11 removal is blocked, revealing the regulatory logic of Spo11 targeting and turnover.

    Evidence Chromatin immunoprecipitation with active-site and DSB-factor mutant epistasis in yeast

    PMID:15655113

    Open questions at the time
    • Genome-wide DSB landscape at base resolution not yet mapped
    • Mechanism of Spo11 removal from DNA not resolved
    • Axis-loop connection to Spo11 targeting unclear
  6. 2007 High

    Whether Spo11 acts as a dimer in vivo was unresolved; co-immunoprecipitation of differentially tagged Spo11 proteins demonstrated self-association dependent on Rec102/Rec104/Rec114, and a catalytic-dead heterodimer failed to cleave, establishing that dimerization is essential for DSB catalysis.

    Evidence In vivo co-IP of distinctly tagged Spo11, Gal4BD-Spo11 targeting assay, Y135F active-site mutation

    PMID:17264124

    Open questions at the time
    • Whether one or both protomers contribute active-site residues not resolved
    • Quaternary structure of the full complex unknown
    • Dimerization trigger not identified
  7. 2009 High

    The mechanism by which Spo11 is removed from DSB ends was unknown; detection of Spo11/Rec12-oligonucleotide complexes requiring Mre11 nuclease activity, Rad50, and Ctp1/Sae2 established that endonucleolytic cleavage by the MRN-Sae2 axis liberates Spo11, and that Spo11 has intrinsic sequence preference in site selection.

    Evidence Biochemical detection of Spo11-oligo complexes with nuclease-dead mutants; single-nucleotide resolution DSB mapping with Gal4BD-Spo11

    PMID:19380488 PMID:19752195

    Open questions at the time
    • Structural basis of sequence preference unknown
    • Regulation of MRN activation at Spo11-bound ends unclear
    • Oligo length distribution not yet interpreted mechanistically
  8. 2009 High

    How Spo11 distribution along chromosomes is organized was unclear; genome-wide ChIP showed that meiotic cohesin Rec8 guides Spo11 localization, with Spo11 initially accumulating near centromeres then redistributing to arms, linking chromosome architecture to DSB patterning.

    Evidence Genome-wide ChIP-chip for Spo11 with Rec8 deletion mutant analysis in yeast

    PMID:19439448

    Open questions at the time
    • Mechanism of Spo11 redistribution from centromeres to arms not explained
    • Axis-loop tethering model not yet formulated
  9. 2011 High

    How DSB-promoting factors connect chromatin loops to chromosome axes was unknown; ChIP-chip revealed that Rec114/Mei4/Mer2 are tethered to axis sites via Red1/Hop1 and S-phase CDK phosphorylation of Mer2, establishing the tethered-loop/axis model for Spo11-mediated DSB formation.

    Evidence Genome-wide ChIP-chip for Rec114/Mer2/Mei4 with phospho-mutant and axis deletion epistasis in yeast

    PMID:21816273

    Open questions at the time
    • Direct physical contact between axis-tethered factors and Spo11 core complex not demonstrated
    • Temporal regulation of tethering not resolved
    • How tethering controls DSB number unknown
  10. 2013 High

    Whether Spo11 has functions beyond DSB catalysis was unknown; a catalytic-dead SPO11 mutant in mice supported pre-DSB homolog pairing (dependent on SUN1), and Spo11 was shown to be required for γH2AX on XY chromatin, revealing DSB-independent roles in chromosome dynamics.

    Evidence Catalytic-dead Spo11 mutant mice, FISH-based pairing assay, SUN1 epistasis, γH2AX immunofluorescence

    PMID:15998665 PMID:23318132

    Open questions at the time
    • Molecular mechanism of DSB-independent pairing function unknown
    • Whether the pairing function involves DNA binding is untested
    • Structural basis of this non-catalytic role unresolved
  11. 2020 High

    How SPO11 processing is locally regulated at hotspots was unclear; END-seq revealed that PRDM9 asymmetrically blocks MRE11-mediated SPO11 release, generating a trapped SPO11-bound recombination intermediate, while ATM is required for efficient initiation of SPO11 removal, identifying the key local regulators of SPO11 processing.

    Evidence END-seq on mouse spermatocytes with enzymatic modification to detect SPO11-bound intermediates; Atm−/− analysis

    PMID:32051414

    Open questions at the time
    • Structural basis of PRDM9-imposed asymmetry unknown
    • Whether other chromatin features contribute to asymmetric processing untested
    • Interplay between ATM-mediated feedback and SPO11 dosage incompletely understood
  12. 2021 High

    The biochemical composition and DNA-binding properties of the Spo11 core complex were unresolved; reconstitution showed a monomeric 1:1:1:1 Spo11-Rec102-Rec104-Ski8 complex where Rec102-Rec104 resemble Top6B, with preference for duplex junctions and DNA ends, and cryo-EM later revealed metal-dependent backbone contacts and end-binding specificity determinants.

    Evidence Purification and SEC-MALS of yeast Spo11 core complex; DNA-binding assays with mutagenesis; cryo-EM at 3.3 Å resolution

    PMID:33398171 PMID:39304764

    Open questions at the time
    • Structure of the dimeric cleavage-competent complex not yet determined
    • How accessory factors activate the core complex structurally unresolved
    • Cryo-EM of the pre-cleavage DNA-engaged dimer missing
  13. 2021 High

    Whether Spo11 can make concerted double cuts and what governs cleavage geometry was unknown; genome-wide mapping revealed Spo11 generates paired DSBs with ~10.5-bp periodicity indicating helical-face-constrained cleavage of underwound DNA, with overlap at topoisomerase II binding sites implicating DNA topology in break site selection.

    Evidence High-resolution sequencing of Spo11 double-cut fragments in yeast and mouse; overlap with Topo II ChIP sites

    PMID:34108684 PMID:34108687

    Open questions at the time
    • Mechanism coupling DNA topology to Spo11 cleavage not demonstrated biochemically
    • Whether gap-initiated recombination uses a distinct repair pathway unknown
    • Relationship between double cuts and Spo11-oligo size classes not fully explained
  14. 2021 High

    A potential non-catalytic role for Spo11 in centromere remodeling was unknown; Spo11 together with Rec8 was shown to dismantle centromeres when the telomere bouquet is absent, and ectopic expression in mitotic cells destroys kinetochores, revealing a structural role in centromere dynamics.

    Evidence Overexpression in fission yeast and human cells, bouquet mutant epistasis, kinetochore marker immunofluorescence

    PMID:33658710

    Open questions at the time
    • Mechanism of centromere dismantling unknown
    • Whether this involves DNA cleavage or a structural role untested
    • Physiological relevance during normal meiosis not fully established
  15. 2024 High

    Whether Spo11 directly recruits the DSB repair machinery was unclear; the Spo11 C-terminal region was found to physically interact with Mre11, promoting Mre11 chromatin recruitment and stimulating its nuclease activity independently of DSB formation, establishing a direct link between DSB formation and repair initiation.

    Evidence Purified Spo11 fragments, in vitro interaction and nuclease stimulation assays, calibrated ChIP in yeast

    PMID:38407383

    Open questions at the time
    • Whether the Spo11-Mre11 interaction is conserved in mammals not tested
    • Structural basis of the interaction unknown
    • How this interaction is temporally regulated relative to DSB formation unclear
  16. 2025 High

    Full in vitro reconstitution of SPO11-dependent DSB activity had never been achieved; purified mouse SPO11 (alone or with TOP6BL) was shown to catalyze covalent DNA cleavage requiring active-site tyrosine, divalent metals, and dimerization, with cleavage influenced by DNA sequence, bendability, and topology, and SPO11 can reseal nicks, completing the biochemical characterization of the core catalytic mechanism.

    Evidence In vitro reconstitution with purified recombinant mouse SPO11 and SPO11-TOP6BL; active-site and dimerization mutant analysis; DNA topology assays; AlphaFold3 modeling

    PMID:39972129 PMID:39972130

    Open questions at the time
    • How accessory factors (Rec114/Mei4/Mer2 equivalents) activate the core complex in vitro not reconstituted
    • Full-length dimeric complex structure not yet solved experimentally
    • Regulation of cleavage-religation balance in vivo unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: how the transition from monomeric core complex to cleavage-competent dimer is regulated in vivo, the structural basis of axis-tethered accessory factor activation of the core complex, and the molecular mechanism underlying SPO11's DSB-independent roles in homolog pairing and centromere remodeling.
  • No structure of the activated dimeric Spo11 complex on DNA
  • Mechanism of DSB-independent pairing function completely uncharacterized at molecular level
  • How feedback from ATM calibrates DSB number through Spo11 activity not fully resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 4
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 4 GO:0000228 nuclear chromosome 3 R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 3
Partners
MRE11PRDM9REC102REC104REC114REC8SKI8TOP6BL
Complex memberships
MRN complex (functional interaction)Spo11 core complex (Spo11-Rec102/TOP6BL-Rec104-Ski8)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Spo11 is the catalytic subunit of the meiotic DNA double-strand break (DSB) cleavage activity; it becomes covalently attached to the 5' ends of DSBs via a topoisomerase-like transesterase mechanism, as demonstrated by purification of protein-DNA complexes from yeast meiotic cells and identification of Spo11 as the covalently bound protein. Biochemical purification of protein-DNA complexes from meiotic yeast cells; identification of Spo11 as the covalently attached protein Cell High 9039264
1999 The archaeal topoisomerase VI A (Top6A) subunit, the structural homolog of Spo11, forms a dimer with a deep groove spanning both protomers where DNA is bound; the crystal structure reveals shared domain architecture with type IA and classic type II topoisomerases, providing a structural template for Spo11 function. X-ray crystallography at 2.0 Å resolution of Methanococcus jannaschii Top6A DNA-binding core The EMBO journal High 10545127
2000 Mouse Spo11 is required for meiotic DSB formation (no Rad51/Dmc1 foci detected in Spo11-/- spermatocytes) and for homologous chromosome synapsis; cisplatin-induced DSBs in Spo11-/- cells restore Rad51/Dmc1 foci and promote synapsis, demonstrating that DSBs are the required trigger for synapsis. Mouse Spo11 gene disruption (knockout), immunofluorescence for Rad51/Dmc1 foci, cisplatin rescue experiment, meiotic chromosome spreads Molecular cell High 11106738
2000 Mouse Spo11 disruption abolishes Dmc1/Rad51 focus formation and causes homologous chromosome synapsis defects, establishing that recombination initiation by Spo11 precedes and is required for normal synapsis in mammals; meiotic checkpoint responses to recombination/synapsis defects are sexually dimorphic. Mouse Spo11 knockout, immunofluorescence for Dmc1/Rad51, meiotic chromosome spread analysis Molecular cell High 11106739
2004 Ski8 is a direct binding partner of Spo11 in meiotic DSB formation, independent of its cytoplasmic RNA metabolism role; Ski8 relocalizes to the nucleus and associates with chromosomes specifically during meiosis, its interaction with Spo11 is essential for DSB formation, and it acts as a scaffold to recruit other DSB proteins to meiotic chromosomes. Two-hybrid analysis, co-immunoprecipitation, chromosome spread localization, genetic epistasis (ski8 mutant DSB assay) Molecular cell High 14992724
2002 Spo11 physically interacts with Rec102 in vivo (co-immunoprecipitation from meiotic extracts), and Rec102 is required for Spo11's association with meiotic chromatin; tagged Rec102 localizes to the nucleus and to chromatin on spread meiotic chromosomes, consistent with a multiprotein DSB complex containing both Spo11 and Rec102. Co-immunoprecipitation from meiotic cell extracts, chromosome spread immunofluorescence, synthetic conditional phenotype analysis Genetics High 11805049
2005 Spo11 transiently and noncovalently associates with meiotic recombination hotspots in wild-type yeast; this association requires Rec102, Rec104, and Rec114, and timely removal requires Mei4 and Ndt80; Red1 restricts Spo11's interaction to the hotspot core region. In rad50S and com1Δ/sae2Δ mutants, a reversible Spo11 cleavage intermediate is detectable that requires the catalytic residue Y135. Chromatin immunoprecipitation (ChIP), epistasis analysis with DSB-factor deletion mutants, active-site mutation (Y135) Genes & development High 15655113
2007 Spo11 self-associates (dimerizes) in vivo during meiosis at the time of DSB formation; this self-interaction requires Rec102, Rec104, and Rec114. A Gal4BD-Spo11 fusion can recruit Spo11-3FLAG to the GAL2 locus, but nuclease-deficient Spo11-Y135F in a heterocomplex does not support cleavage. In vivo co-immunoprecipitation of distinctly tagged Spo11 proteins, Gal4BD-Spo11 targeting assay, active-site mutation (Y135F) Nucleic acids research High 17264124
2009 Spo11 is endonucleolytically released from DSB ends covalently attached to a short oligonucleotide (Spo11-oligonucleotide complex); in fission yeast, generation of Rec12-oligonucleotide complexes strictly requires Ctp1 (Sae2 homolog), the Rad32 (Mre11) nuclease domain, and Rad50, with Rad32 proposed as the catalytic nuclease activated by Ctp1. Biochemical detection of Spo11/Rec12-oligonucleotide complexes, nuclease-dead Mre11 mutant analysis, genetic requirement assay Molecular and cellular biology High 19752195
2009 Rec8 (meiotic cohesin) guides the canonical distribution of Spo11 along yeast meiotic chromosomes: Spo11 initially accumulates around centromeres then redistributes to arm regions; a substantial proportion of Spo11 binding overlaps with Rec8 binding sites, and deletion of REC8 alters Spo11 localization and DSB formation in a region-specific manner. Genome-wide ChIP-chip (tiling arrays) for Spo11, Rec8 deletion mutant analysis Molecular biology of the cell High 19439448
2011 Spo11-accessory proteins Rec114, Mer2, and Mei4 stably interact with chromosome axis sequences (axis tethering), requiring meiotic axis components Red1/Hop1 and Mer2 phosphorylation by S-phase Cdk; this axis tethering correlates with DSB formation, suggesting that hotspot sequences become tethered to axis sites by the DSB machinery prior to DSB formation. ChIP-chip in yeast for Rec114/Mer2/Mei4, phospho-mutant analysis, deletion epistasis with Red1/Hop1/cohesin Cell High 21816273
2013 SPO11 is strictly required for H2AX phosphorylation in the XY chromatin and for sex body (XY body) formation in mouse spermatocytes; Spo11 heterozygosity rescues the prophase-I arrest of ATM-deficient spermatocytes by halving the number of unrepaired DSBs, placing Spo11 upstream of ATM in the meiotic DSB signaling pathway. Spo11 knockout and heterozygous mice, Atm-/- Spo11+/- double mutant analysis, immunofluorescence for γH2AX, ATR co-localization Journal of cell science High 15998665
2013 In mouse, a significant level of homolog pairing precedes SPO11-mediated DSBs; this pre-DSB pairing still requires SPO11 but is independent of its DSB-forming catalytic activity (demonstrated using a catalytic-dead SPO11 mutant) and requires SUN1 (a telomere attachment protein). Spo11 knockout and catalytic mutant mice, FISH-based homolog pairing assay, SUN1 mutant epistasis Developmental cell High 23318132
2020 PRDM9 asymmetrically blocks MRE11-mediated release of SPO11 from DSB ends, generating a SPO11-bound recombination intermediate (SPO11-RI) at all hotspots; in ATM-deficient spermatocytes, trapped SPO11 cleavage complexes accumulate due to defective MRE11 initiation of resection, establishing that ATM and PRDM9 are critical local regulators of SPO11 processing. END-seq on mouse spermatocytes, enzymatic modifications to detect SPO11-RI, Atm-/- spermatocyte analysis Nature communications High 32051414
2021 Spo11 generates concerted (double) DSBs separated by 33 to >100 bp with a periodicity of ~10.5 bp, indicating that adjacent Spo11 molecules are oriented at fixed positions relative to the DNA helix; the Spo11 core complex binds DNA in vitro consistent with this geometry, and double-cut-generated gaps can initiate recombination independently. High-resolution mapping of Spo11 double-cut fragments in yeast and mice; in vitro DNA-binding assay of purified Spo11 core complex; deep sequencing of meiotic recombination products Nature High 34108687
2021 Spo11 generates gaps (34 to several hundred bp) by coordinated pairs of DSBs (double DSBs); fragment lengths show ~10.4n+3 bp periodicity indicating cleavage on the same face of underwound DNA; double DSB signals overlap with topoisomerase II binding sites, suggesting topological stress and DNA crossings promote break formation. Isolation and genome-wide mapping of double-DSB fragments at single-base-pair resolution; overlap analysis with Topo II binding sites Nature High 34108684
2021 Purified Saccharomyces cerevisiae Spo11 with partners Rec102, Rec104, and Ski8 forms a monomeric 1:1:1:1 complex; Rec102 and Rec104 jointly resemble the Top6B subunit, with Rec104 occupying the GHKL ATPase domain position; the complex binds DNA with topoisomerase-like preference for duplex-duplex junctions and bent DNA, and binds DNA ends with high affinity (cap model); mutations reducing DNA binding in vitro attenuate DSB formation and reshape the DSB landscape in vivo. Purification and reconstitution of Spo11 core complex; SEC-MALS stoichiometry determination; DNA-binding assays; active-site and DNA-binding mutations; in vivo DSB mapping Nature structural & molecular biology High 33398171
2021 Spo11 and the meiotic cohesin Rec8 can dismantle centromeres; this activity requires specific nucleosome remodeling factors and is normally observable only when the telomere bouquet is absent; ectopic Spo11 or Rec8 expression in proliferating fission yeast and human cells leads to loss of mitotic kinetochores. Overexpression in fission yeast and human cells, genetic epistasis with bouquet mutants, immunofluorescence for kinetochore markers Nature High 33658710
2024 Cryo-EM structures of the S. cerevisiae Spo11 core complex (Spo11-Rec102-Rec104-Ski8) bound to DNA at up to 3.3-Å resolution reveal that monomeric core complexes make extensive contacts with the DNA backbone and with the recessed 3'-OH and first 5' overhanging nucleotide, establishing the molecular determinants of DNA end-binding specificity and providing insight into cleavage preferences; metal ions are required for DNA binding. Cryo-electron microscopy structure determination; functional validation by site-directed mutagenesis in yeast Nature structural & molecular biology High 39304764
2024 Spo11 physically interacts with Mre11 via its far C-terminal region; this interaction promotes Mre11 recruitment to meiotic chromatin independent of DSB formation and stimulates Mre11 DNA binding, bridging, and nuclease activities; a Spo11 mutant deficient in Mre11 interaction severely reduces Mre11 chromatin association and DSB formation. Purification of Spo11 fragments, in vitro protein interaction assay, Mre11 activity assays, calibrated ChIP for Mre11, in vivo spore viability Nucleic acids research High 38407383
2025 Reconstitution of SPO11-dependent DSB formation in vitro with purified recombinant mouse SPO11 bound to TOP6BL; SPO11-TOP6BL complexes are monomeric (1:1) in solution and bind DNA tightly, but dimeric (2:2) assemblies catalyze DNA cleavage forming covalent 5' attachments requiring the SPO11 active-site residues, divalent metal ions, and SPO11 dimerization; SPO11 can also reseal nicked DNA; cleavage is influenced by DNA sequence, bendability and topology; AlphaFold3 modelling suggests DNA bending precedes cleavage. In vitro reconstitution with purified recombinant mouse SPO11-TOP6BL; active-site mutagenesis; dimerization assay; DNA topology and sequence bias analysis; AlphaFold3 structural modelling Nature High 39972129
2025 Purified mouse SPO11 alone (without any partners) catalyzes DSBs in vitro; SPO11 is monomeric in solution and requires dimerization to reconstitute two hybrid active sites for cleavage; SPO11 can reseal single-strand DNA breaks; target site selection is influenced by DNA sequence, bendability and topology; SPO11-TOP6BL forms a 1:1 complex that cleaves with similar activity to SPO11 alone but binds DNA ends with higher affinity. In vitro DSB reconstitution with purified mouse SPO11; biochemical and biophysical characterization of SPO11 and SPO11-TOP6BL complexes; active-site and dimerization mutant analysis Nature High 39972130
2009 Spo11 locally introduces DSBs at discrete sites with sequence preference; using Gal4BD-Spo11, breaks are restricted to a ~20-nucleotide DSB targeting window from the Gal4 UAS; mutations in the Spo11 moiety and in the DNA at cleavage sites alter DSB position, demonstrating that Spo11 has intrinsic sequence preference contributing to cleavage site choice. Single-nucleotide resolution mapping of Gal4BD-Spo11-targeted DSBs; site-directed mutagenesis of Spo11 and DNA substrate Molecular and cellular biology High 19380488
2020 SPO11-regulated alternative splicing during mouse meiosis is controlled by combinatorial action of hnRNPH (promoting SPO11α/exon 2 skipping) and Sam68 (promoting SPO11β/exon 2 inclusion); hnRNPH competes with Sam68 for Spo11 pre-mRNA binding; modulation of RNA polymerase II phosphorylation and processivity near exon 2 regulates hnRNPH recruitment. Spo11 pre-mRNA splicing reporter assay, RIP (RNA immunoprecipitation), siRNA knockdown, RNAPII phosphorylation analysis in mouse spermatocytes Cell death & disease Medium 32303676
2023 FUS/TLS physically interacts with SPO11 (both splice isoforms) in vitro and in vivo, and also interacts with PRDM9 and the SPO11-auxiliary factor REC114; FUS/TLS localizes to H3K4me3-marked recombination hotspots in autosomes and in the pseudoautosomal region, suggesting it is a component of the DSB initiation complex. Co-immunoprecipitation (in vitro and in vivo), chromatin immunoprecipitation (ChIP), immunofluorescence on meiotic chromosome spreads Cellular and molecular life sciences Medium 36967403
1998 Drosophila mei-W68 encodes an Spo11 homolog required for all meiotic gene conversion and crossing-over, but unlike yeast Spo11, is not required for synaptonemal complex formation and has a mitotic role, demonstrating evolutionary conservation of the mechanism of recombination initiation but divergence in its coupling to synapsis. Genetic cloning by P-element mapping, sequencing of mei-W68 mutants, meiotic recombination and SC formation analysis Genes & development High 9744869
2004 In Arabidopsis, double mutant analysis (mre11 spo11-1) shows that chromosome fragmentation in mre11 mutants is substantially suppressed by spo11-1, demonstrating that MRE11 is required for repair but not induction of Spo11-dependent meiotic DSBs. Double mutant epistasis (mre11 spo11-1), cytogenetic analysis of pollen mother cells The Plant cell Medium 15258261
2007 Both AtSPO11-1 and AtSPO11-2 catalytically active tyrosine residues are required for meiotic DSB induction in Arabidopsis; constructs mutated at the respective catalytic Tyr fail to complement meiotic phenotypes of single mutants, and the spo11-1 spo11-2 double mutant is not additive, indicating both proteins are required for the same DSB-forming step. Catalytic-site mutagenesis (Tyr→ non-functional), in vivo complementation assay, double mutant analysis The Plant cell High 17965269

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 1445 9039264
2000 The mouse Spo11 gene is required for meiotic chromosome synapsis. Molecular cell 637 11106738
2000 Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Molecular cell 570 11106739
2011 Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination. Cell 296 21816273
2008 Spo11 and the Formation of DNA Double-Strand Breaks in Meiosis. Genome dynamics and stability 254 21927624
1998 mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved. Genes & development 229 9744869
1985 The role of the SPO11 gene in meiotic recombination in yeast. Genetics 225 3891509
2006 Arabidopsis SPO11-2 functions with SPO11-1 in meiotic recombination. The Plant journal : for cell and molecular biology 172 17018031
2005 SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes. Journal of cell science 162 15998665
2004 Mre11 deficiency in Arabidopsis is associated with chromosomal instability in somatic cells and Spo11-dependent genome fragmentation during meiosis. The Plant cell 162 15258261
1999 Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo11. The EMBO journal 148 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 140 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 121 23318132
2007 The catalytically active tyrosine residues of both SPO11-1 and SPO11-2 are required for meiotic double-strand break induction in Arabidopsis. The Plant cell 117 17965269
2000 Multiple roles of Spo11 in meiotic chromosome behavior. The EMBO journal 110 10835371
2000 Molecular characterisation of two paralogous SPO11 homologues in Arabidopsis thaliana. Nucleic acids research 99 10710421
2020 ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis. Nature communications 95 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 87 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 82 15655113
2010 Evolutionary conservation of meiotic DSB proteins: more than just Spo11. Genes & development 73 20551169
2021 Concerted cutting by Spo11 illuminates meiotic DNA break mechanics. Nature 68 34108687
2013 SPO11-independent DNA repair foci and their role in meiotic silencing. PLoS genetics 67 23754961
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 51 10973500
2021 Spo11 generates gaps through concerted cuts at sites of topological stress. Nature 48 34108684
2007 Meiotic association between Spo11 regulated by Rec102, Rec104 and Rec114. Nucleic acids research 48 17264124
2003 The Arabidopsis MEI1 gene encodes a protein with five BRCT domains that is involved in meiosis-specific DNA repair events independent of SPO11-induced DSBs. The Plant journal : for cell and molecular biology 44 12904209
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
2011 OsSpo11-4, a rice homologue of the archaeal TopVIA protein, mediates double-strand DNA cleavage and interacts with OsTopVIB. PloS one 36 21637817
2020 NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis. Cell death and differentiation 35 31965061
2017 Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11. eLife 34 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 28 32310948
2016 Atypical ploidy cycles, Spo11, and the evolution of meiosis. Seminars in cell & developmental biology 28 26811992
2020 SPO11.2 is essential for programmed double-strand break formation during meiosis in bread wheat (Triticum aestivum L.). The Plant journal : for cell and molecular biology 27 32603485
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
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
2004 Meiotic chromosome synapsis in yeast can occur without spo11-induced DNA double-strand breaks. Genetics 24 15514052
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
2017 Tex19.1 promotes Spo11-dependent meiotic recombination in mouse spermatocytes. PLoS genetics 22 28708824
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
2021 Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8. Nature 21 33658710
2000 Identification and characterization of an SPO11 homolog in the mouse. Chromosoma 21 10855504
2025 Reconstitution of SPO11-dependent double-strand break formation. Nature 18 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
2025 SPO11 dimers are sufficient to catalyse DNA double-strand breaks in vitro. Nature 17 39972130
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 A DNA-binding surface of SPO11-1, an Arabidopsis SPO11 orthologue required for normal meiosis. The FEBS journal 17 20423461
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
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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
2023 Conserved meiotic mechanisms in the cnidarian Clytia hemisphaerica revealed by Spo11 knockout. Science advances 13 36706182
2013 Suppression of genetic recombination in the pseudoautosomal region and at subtelomeres in mice with a hypomorphic Spo11 allele. BMC genomics 13 23870400
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
2013 A mutation in the FHA domain of Coprinus cinereus Nbs1 Leads to Spo11-independent meiotic recombination and chromosome segregation. G3 (Bethesda, Md.) 12 24062528
2004 Purification, folding, and characterization of Rec12 (Spo11) meiotic recombinase of fission yeast. Protein expression and purification 12 15477092
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2022 Differentiated function and localisation of SPO11-1 and PRD3 on the chromosome axis during meiotic DSB formation in Arabidopsis thaliana. PLoS genetics 11 35857772
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
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
2023 Plasmodium Topoisomerase VIB and Spo11 Constitute Functional Type IIB Topoisomerase in Malaria Parasite: Its Possible Role in Mitochondrial DNA Segregation. Microbiology spectrum 5 37212694
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