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Gene Review

SPO11  -  Spo11p

Saccharomyces cerevisiae S288c

Synonyms: Meiosis-specific protein SPO11, Sporulation-specific protein 11, YHL022C
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Disease relevance of SPO11


High impact information on SPO11

  • Meiotic recombination in Saccharomyces cerevisiae is initiated by programmed DNA double-strand breaks (DSBs), a process that requires the Spo11 protein [2].
  • We report that a Spo11 construct bearing the Gal4 DNA binding domain not only rescues spo11Delta spore inviability and catalyzes DSB formation at natural sites but also strongly stimulates DSB formation near Gal4 binding sites [2].
  • In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis [3].
  • Using mutations affecting the initiation of recombination (spo11) or mismatch repair (msh2 pms1 ), we demonstrate that meiotic destabilization depends on the initiation of homologous recombination at nearby DNA double-strand break (DSBs) sites and involves a 'rearranged heteroduplex' intermediate [4].
  • These findings strongly implicate Spo11 as the catalytic subunit of the meiotic DNA cleavage activity [5].

Biological context of SPO11

  • Deletion of the SPO11 gene decreases the length of S phase by approximately 25% [6].
  • The ume3-1 allele was identified as a mutation that allowed the aberrant expression of several meiotic genes (e.g. SPO11, SPO13) during mitotic cell division in Saccharomyces cerevisiae [7].
  • The specificity is achieved by selecting for mutants that produce viable spores when recombination and reductional segregation are prevented by mutations in SPO11 and SPO13 genes, but fail to yield viable spores during a normal Rec+ meiosis [8].
  • The mutations of interest confer a defect in spore formation that is dependent upon a gene required for initiation of meiotic recombination and development of meiosis-specific chromosome structure (SPO11) [9].
  • This conditional defect could be partially rescued by expression of untagged SPO11, but not by expression of untagged REC102, indicating that tagged REC102 is fully dominant for this synthetic phenotype [10].

Anatomical context of SPO11


Associations of SPO11 with chemical compounds

  • Mutagenesis, performed on SPO11, of the single tyrosine conserved between the five homologues shows that this amino acid is essential for Spo11 activity [13].
  • Mutations at an invariant arginine (Arg-131) within a second conserved structural motif known as the 5Y-CAP domain, as well as three other mutations (E235A, F260R, and D290A), caused marked changes in the DSB pattern at a recombination hotspot, suggesting that Spo11p contributes directly to the choice of DNA cleavage site [14].
  • These Toprim domain residues have been implicated in binding a metal ion cofactor in topoisomerases and bacterial primases, supporting the idea that DNA cleavage by Spo11p is Mg(2+) dependent [14].

Physical interactions of SPO11


Enzymatic interactions of SPO11


Regulatory relationships of SPO11


Other interactions of SPO11

  • We find that double-strand breaks occur at two specific sites associated with the hot spot and that occurrence of these breaks depends upon meiotic recombination functions RAD50 and SPO11 [19].
  • We report that Mre11p transiently associates with the chromatin of Spo11-dependent DSB regions throughout the genome [20].
  • Analysis of the spo11 mutant demonstrates that Red1 localization does not depend upon meiotic recombination [21].
  • This study demonstrates genetic and physical interactions between the products of SPO11 and another early meiotic gene required for DSB formation, REC102 [10].
  • If DSB formation is blocked (e.g., by a spo11 mutation), dephosphorylation of Mer2 and its dissociation from chromosomes are delayed [22].

Analytical, diagnostic and therapeutic context of SPO11


  1. The mouse Spo11 gene is required for meiotic chromosome synapsis. Romanienko, P.J., Camerini-Otero, R.D. Mol. Cell (2000) [Pubmed]
  2. Targeted stimulation of meiotic recombination. Peciña, A., Smith, K.N., Mézard, C., Murakami, H., Ohta, K., Nicolas, A. Cell (2002) [Pubmed]
  3. Recombinational DNA double-strand breaks in mice precede synapsis. Mahadevaiah, S.K., Turner, J.M., Baudat, F., Rogakou, E.P., de Boer, P., Blanco-Rodríguez, J., Jasin, M., Keeney, S., Bonner, W.M., Burgoyne, P.S. Nat. Genet. (2001) [Pubmed]
  4. Meiotic instability of human minisatellite CEB1 in yeast requires DNA double-strand breaks. Debrauwère, H., Buard, J., Tessier, J., Aubert, D., Vergnaud, G., Nicolas, A. Nat. Genet. (1999) [Pubmed]
  5. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Keeney, S., Giroux, C.N., Kleckner, N. Cell (1997) [Pubmed]
  6. Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p. Cha, R.S., Weiner, B.M., Keeney, S., Dekker, J., Kleckner, N. Genes Dev. (2000) [Pubmed]
  7. Stress and developmental regulation of the yeast C-type cyclin Ume3p (Srb11p/Ssn8p). Cooper, K.F., Mallory, M.J., Smith, J.B., Strich, R. EMBO J. (1997) [Pubmed]
  8. Isolation of COM1, a new gene required to complete meiotic double-strand break-induced recombination in Saccharomyces cerevisiae. Prinz, S., Amon, A., Klein, F. Genetics (1997) [Pubmed]
  9. A general method for identifying recessive diploid-specific mutations in Saccharomyces cerevisiae, its application to the isolation of mutants blocked at intermediate stages of meiotic prophase and characterization of a new gene SAE2. McKee, A.H., Kleckner, N. Genetics (1997) [Pubmed]
  10. Functional interactions between SPO11 and REC102 during initiation of meiotic recombination in Saccharomyces cerevisiae. Kee, K., Keeney, S. Genetics (2002) [Pubmed]
  11. A mouse homolog of the Saccharomyces cerevisiae meiotic recombination DNA transesterase Spo11p. Keeney, S., Baudat, F., Angeles, M., Zhou, Z.H., Copeland, N.G., Jenkins, N.A., Manova, K., Jasin, M. Genomics (1999) [Pubmed]
  12. Differential gene expression of mammalian SPO11/TOP6A homologs during meiosis. Shannon, M., Richardson, L., Christian, A., Handel, M.A., Thelen, M.P. FEBS Lett. (1999) [Pubmed]
  13. An atypical topoisomerase II from Archaea with implications for meiotic recombination. Bergerat, A., de Massy, B., Gadelle, D., Varoutas, P.C., Nicolas, A., Forterre, P. Nature (1997) [Pubmed]
  14. Identification of residues in yeast Spo11p critical for meiotic DNA double-strand break formation. Diaz, R.L., Alcid, A.D., Berger, J.M., Keeney, S. Mol. Cell. Biol. (2002) [Pubmed]
  15. Support for a meiotic recombination initiation complex: interactions among Rec102p, Rec104p, and Spo11p. Jiao, K., Salem, L., Malone, R. Mol. Cell. Biol. (2003) [Pubmed]
  16. The structure of Ski8p, a protein regulating mRNA degradation: Implications for WD protein structure. Madrona, A.Y., Wilson, D.K. Protein Sci. (2004) [Pubmed]
  17. VDE-initiated intein homing in Saccharomyces cerevisiae proceeds in a meiotic recombination-like manner. Fukuda, T., Nogami, S., Ohya, Y. Genes Cells (2003) [Pubmed]
  18. HO endonuclease-induced recombination in yeast meiosis resembles Spo11-induced events. Malkova, A., Klein, F., Leung, W.Y., Haber, J.E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae. Cao, L., Alani, E., Kleckner, N. Cell (1990) [Pubmed]
  20. Association of Mre11p with double-strand break sites during yeast meiosis. Borde, V., Lin, W., Novikov, E., Petrini, J.H., Lichten, M., Nicolas, A. Mol. Cell (2004) [Pubmed]
  21. The yeast Red1 protein localizes to the cores of meiotic chromosomes. Smith, A.V., Roeder, G.S. J. Cell Biol. (1997) [Pubmed]
  22. Saccharomyces cerevisiae Mer2, Mei4 and Rec114 form a complex required for meiotic double-strand break formation. Li, J., Hooker, G.W., Roeder, G.S. Genetics (2006) [Pubmed]
  23. The control of Spo11's interaction with meiotic recombination hotspots. Prieler, S., Penkner, A., Borde, V., Klein, F. Genes Dev. (2005) [Pubmed]
  24. 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. Tokuyama, H., Tokuyama, Y. Cell. Immunol. (2000) [Pubmed]
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