Spo11

SPO11
Identifiers
Aliases	SPO11 , CT35, SPATA43, TOPVIA, initiator of meiotic double stranded breaks, SPO11 initiator of meiotic double stranded breaks, Meiotic recombination, Spo11, Meiotic_Spo11, IPR013048, Spo11, TOPOVIA
External IDs	OMIM: 605114 MGI: 1349669 HomoloGene: 6059 GeneCards: SPO11
Gene location (Human) Chr. Chromosome 20 (human) [1] Band 20q13.31 Start 57,329,803 bp [1] End 57,343,994 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2 H3|2 95.64 cM Start 172,819,493 bp [2] End 172,835,369 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in duodenum muscle muscle monocyte muscle of leg ovary lower leg triceps surae gastrocnemius muscle thoracic aorta Top expressed in spermatocyte seminiferous tubule thymus spermatid Paneth cell hair follicle ovary lip superior frontal gyrus skin of back More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion binding catalytic activity hydrolase activity ATP binding protein binding isomerase activity DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity endodeoxyribonuclease activity, producing 3'-phosphomonoesters DNA binding Cellular component chromosome telomere nucleus nuclear chromosome Biological process protein localization to chromosome female gamete generation meiotic telomere clustering male meiosis I DNA metabolic process DNA catabolic process, endonucleolytic oogenesis homologous chromosome pairing at meiosis meiosis synaptonemal complex assembly spermatogenesis spermatid development ovarian follicle development meiotic DNA double-strand break processing meiotic DNA double-strand break formation reciprocal meiotic recombination double-strand break repair involved in meiotic recombination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23626 26972 Ensembl ENSG00000054796 ENSMUSG00000005883 UniProt Q9Y5K1 Q5TCH6 Q9WTK8 RefSeq (mRNA) NM_012444 NM_198265 NM_001083959 NM_001083960 NM_012046 NM_001305434 RefSeq (protein) NP_036576 NP_937998 NP_001077428 NP_001077429 NP_001292363 NP_036176 Location (UCSC) Chr 20: 57.33 – 57.34 Mb Chr 2: 172.82 – 172.84 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Spo11 is a protein that in humans is encoded by the SPO11 gene. Spo11, in a complex with mTopVIB, creates double strand breaks to initiate meiotic recombination. ^{[5] [6]} Its active site contains a tyrosine which ligates and dissociates with DNA to promote break formation. One Spo11 protein is involved per strand of DNA, thus two Spo11 proteins are involved in each double stranded break event.

Genetic exchange between two DNA molecules by homologous recombination can begin with a break in both strands of DNA—called a double-strand break—and recombination is started by an endonuclease enzyme that cuts the DNA molecule that "receives" the exchanged DNA. In meiosis the enzyme is SPO11, which is related to DNA topoisomerases. Topoisomerases change DNA by transiently breaking one or both strands, passing the unbroken DNA strand or strands through the break and repairing the break; the broken ends of the DNA are covalently linked to topoisomerase. SPO11 is similarly attached to the DNA when it forms double-strand breaks during meiosis. ^[7]

Meiotic recombination

SPO11 is considered to play a predominant role in initiating meiotic recombination. However, recombination may also occur by alternative SPO11-independent mechanisms that can be studied experimentally using spo11 mutants.

In the budding yeast Saccharomyces cerevisiae, the meiotic defects in recombination and chromosome disjunction of spo11 mutants are alleviated by X-irradiation. ^[8] This finding indicates that X-ray induced DNA damages can initiate crossover recombination leading to proper disjunction independently of SPO11.

In the worm Caenorhabditis elegans, a homolog of spo11 is ordinarily employed in the initiation of meiotic recombination. However, radiation induced-breaks can also initiate recombination in mutants deleted for this spo11 homolog. ^[9]

Deamination of cytosine resulting in the dU:dG mismatch is one of the most common single-base-altering lesions in non-replicating DNA. Spo11 mutants of the fission yeast Schizosaccharomyces pombe and C. elegans undergo meiotic crossover recombination and proper chromosome segregation when dU:dG lesions are produced in their DNA. ^[10] This crossover recombination does not involve the formation of large numbers of double-strand breaks, but does require uracil DNA-glycosylase, an enzyme that removes uracil from the DNA phosphodiester backbone and initiates base excision repair. Thus, it was proposed that base excision repair of DNA damage such as a uracil base, an abasic site, or a single-strand nick is sufficient to initiate meiotic crossover recombination in S. pombe and C. elegans. ^[10]

In S. pombe, a mutant defective in the spo11 homolog Rec12 is deficient in meiotic recombination. However recombination can be restored to near normal levels by a deletion in rad2, a gene that encodes an endonuclease involved in Okazaki fragment processing (Farah et al., 2005). Both crossover and non-crossover recombination were increased but double-strand breaks were undetectable. On the basis of the biochemical properties of the rad2 deletion, it was proposed that meiotic recombination can be initiated by DNA lesions other than double-strand breaks, such as nicks and gaps which accumulate during premeiotic DNA replication when Okasaki fragment processing is deficient. ^[11]

The above findings indicate that DNA damages arising from a variety of sources can be repaired by meiotic recombination and that such a process can occur independently of SPO11.

Absence in some sexual species

The most recent common ancestor of the social amoeba genera Dictyostelium , Polysphondylium and Acytostelium , appears to have lacked the Spo11 gene. ^{[12] [13]} Such an ancestor likely lived several hundred million years ago. ^[14] Dictyostelium discoideum and Polysphondylium pallidum are both capable of meiotic sexual reproduction (see D. discoideum sexual reproduction and P. pallidum sexual reproduction ). Bloomfield ^[12] speculated that dormant cells in the soil might be exposed to many kinds of stress, such as desiccation or radiation, that could induce spontaneous DNA damage. Such damage would make the induction of double-strand breaks by Spo11 redundant for the initiation of recombination during meiosis, and thus explain its absence in this group.

References

1. GRCh38: Ensembl release 89: ENSG00000054796 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000005883 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Vrielynck N, Chambon A, Vezon D, Pereira L, Chelysheva L, De Muyt A, et al. (February 2016). "A DNA topoisomerase VI-like complex initiates meiotic recombination". Science. 351 (6276): 939–43. Bibcode:2016Sci...351..939V. doi:10.1126/science.aad5196. PMID   26917763. S2CID   206643600.
6. Robert T, Nore A, Brun C, Maffre C, Crimi B, Bourbon HM, de Massy B (February 2016). "The TopoVIB-Like protein family is required for meiotic DNA double-strand break formation". Science. 351 (6276): 943–9. Bibcode:2016Sci...351..943R. doi:10.1126/science.aad5309. PMID   26917764. S2CID   9445593.
7. Lewin's Genes X (10th ed.). Jones and Bartlett Publishers, Inc. 2011. pp. 353–354. ISBN   978-0-7637-7992-4.
8. Thorne LW, Byers B (May 1993). "Stage-specific effects of X-irradiation on yeast meiosis". Genetics. 134 (1): 29–42. doi:10.1093/genetics/134.1.29. PMC   1205431 . PMID   8514137.
9. Dernburg AF, McDonald K, Moulder G, Barstead R, Dresser M, Villeneuve AM (August 1998). "Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis". Cell. 94 (3): 387–98. doi: 10.1016/s0092-8674(00)81481-6 . PMID   9708740. S2CID   10198891.
10. Pauklin S, Burkert JS, Martin J, Osman F, Weller S, Boulton SJ, et al. (May 2009). "Alternative induction of meiotic recombination from single-base lesions of DNA deaminases". Genetics. 182 (1): 41–54. doi:10.1534/genetics.109.101683. PMC   2674839 . PMID   19237686.
11. Farah JA, Cromie G, Davis L, Steiner WW, Smith GR (December 2005). "Activation of an alternative, rec12 (spo11)-independent pathway of fission yeast meiotic recombination in the absence of a DNA flap endonuclease". Genetics. 171 (4): 1499–511. doi:10.1534/genetics.105.046821. PMC   1456079 . PMID   16118186.
12. Bloomfield G (June 2016). "Atypical ploidy cycles, Spo11, and the evolution of meiosis". Seminars in Cell & Developmental Biology. 54: 158–64. doi:10.1016/j.semcdb.2016.01.026. PMID   26811992.
13. Malik SB, Pightling AW, Stefaniak LM, Schurko AM, Logsdon JM (August 2007). "An expanded inventory of conserved meiotic genes provides evidence for sex in Trichomonas vaginalis". PLOS ONE. 3 (8): e2879. doi: 10.1371/journal.pone.0002879 . PMC   2488364 . PMID   18663385.
14. Fiz-Palacios O, Romeralo M, Ahmadzadeh A, Weststrand S, Ahlberg PE, Baldauf S (2013). "Did terrestrial diversification of amoebas (amoebozoa) occur in synchrony with land plants?". PLOS ONE. 8 (9): e74374. Bibcode:2013PLoSO...874374F. doi: 10.1371/journal.pone.0074374 . PMC   3770592 . PMID   24040233.