Spo11: Difference between revisions

'''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 [[genetic recombination|recombination]].<ref>{{Citecite journal |last vauthors = Vrielynck|first=Nathalie|last2= N, Chambon|first2=Aurélie|last3= A, Vezon|first3=Daniel|last4= D, Pereira|first4=Lucie|last5= L, Chelysheva|first5=Liudmila|last6= L, De Muyt|first6=Arnaud De|last7=A, Mézard|first7=Christine|last8= C, Mayer|first8=Claudine|last9= C, Grelon M |first9 display-authors =Mathilde|date=2016-02-26 6 | title = A DNA topoisomerase VI–likeVI-like complex initiates meiotic recombination |url=https://science.sciencemag.org/content/351/6276/939| journal = Science |language=en| volume = 351 | issue = 6276 | pages =939–943 939–43 | date = February 2016 | pmid = 26917763 | doi = 10.1126/science.aad5196 |issn bibcode =0036-8075 2016Sci...351..939V |pmid s2cid =26917763 206643600 | url = https://www.science.org/doi/10.1126/science.aad5196 }}</ref><ref>{{Citecite journal |last vauthors = Robert|first= T.|last2=, Nore|first2= A.|last3=, Brun|first3= C.|last4=, Maffre|first4= C.|last5=, Crimi|first5= B.|last6=Guichard|first6=V.|last7=, Bourbon|first7=H.-M.|last8= HM, de Massy|first8= B. de|date=2016-02-26| title = The TopoVIB-Like protein family is required for meiotic DNA double-strand break formation |url=https://science.sciencemag.org/content/351/6276/943| journal = Science |language=en| volume = 351 | issue = 6276 | pages =943–949 943–9 | date = February 2016 | pmid = 26917764 | doi = 10.1126/science.aad5309 |issn bibcode =0036-8075 2016Sci...351..943R |pmid s2cid =26917764 9445593 | url = https://www.science.org/doi/10.1126/science.aad5309 }}</ref> 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]] beginscan 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 [[topoisomerase]]s. 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.<ref name="isbn0-7637-7992-X">{{cite book |title=Lewin's Genes X |edition=10th |publisher=Jones and Bartlett Publishers, Inc. |location= |year=2011 |origyear= |pages=353–354 |isbn=978-0-7637-7992-4 |oclc= |doi= |url= |accessdate=}}</ref>

In the budding yeast ''SacharomycesSaccharomyces cerevisiae'', the meiotic defects in recombination and chromosome disjunction of ''spo11'' mutants are alleviated by X-irradiation.<ref name="pmid8514137">{{cite journal | vauthors = Thorne LW, Byers B | title = Stage-specific effects of X-irradiation on yeast meiosis | journal = Genetics | volume = 134 | issue = 1 | pages = 29–42 |year date = May 1993 | doi = 10.1093/genetics/134.1.29 | pmid = 8514137 | pmc = 1205431 |doi= |url=}}</ref> 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.<ref name="pmid9708740">{{cite journal | vauthors = Dernburg AF, McDonald K, Moulder G, Barstead R, Dresser M, Villeneuve AM | title = Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis | journal = Cell | volume = 94 | issue = 3 | pages = 387–98 |year date = August 1998 | pmid = 9708740 | doi = 10.1016/s0092-8674(00)81481-6 |url s2cid = 10198891 | doi-access = free }}</ref>

[[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.<ref name=Pauklin>{{cite journal | vauthors = Pauklin S, Burkert JS, Martin J, Osman F, Weller S, Boulton SJ, Whitby MC, Petersen-Mahrt SK | display-authors = 6 | title = Alternative induction of meiotic recombination from single-base lesions of DNA deaminases | journal = Genetics | volume = 182 | issue = 1 | pages = 41–54 |year date = May 2009 | pmid = 19237686 | pmc = 2674839 | doi = 10.1534/genetics.109.101683 |url=}}</ref> 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 [[AP site|abasic site]], or a single-strand nick is sufficient to initiate meiotic crossover recombination in ''S. pombe'' and ''C. elegans''.<ref name=Pauklin />

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 fragments|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.<ref name="pmid16118186">{{cite journal | vauthors = Farah JA, Cromie G, Davis L, Steiner WW, Smith GR | title = Activation of an alternative, rec12 (spo11)-independent pathway of fission yeast meiotic recombination in the absence of a DNA flap endonuclease | journal = Genetics | volume = 171 | issue = 4 | pages = 1499–511 |year date = December 2005 | pmid = 16118186 | pmc = 1456079 | doi = 10.1534/genetics.105.046821 |url=}}</ref>

The most recent common ancestor of the social [[amoeba]] genera ''[[Dictyostelium]]'', ''[[Polysphondylium]]'' and ''[[Acytostelium]]'', appears to have lacked the ''Spo11'' gene.<ref name=Bloomfield>{{cite journal | vauthors = Bloomfield G | title = Atypical ploidy cycles, Spo11, and the evolution of meiosis | journal =Semin. Seminars in Cell Dev.& Biol.Developmental Biology | volume = 54 |issue= |pages = 158–64 |year date = June 2016 | pmid = 26811992 | doi = 10.1016/j.semcdb.2016.01.026 | url = https://zenodo.org/record/889469 }}</ref><ref name="pmid18663385">{{cite journal | vauthors = Malik SB, Pightling AW, Stefaniak LM, Schurko AM, Logsdon JM | title = An expanded inventory of conserved meiotic genes provides evidence for sex in Trichomonas vaginalis | journal =PLoS PLOS ONE | volume = 3 | issue = 8 | pages = e2879 |year date = August 2007 | pmid = 18663385 | pmc = 2488364 | doi = 10.1371/journal.pone.0002879 |url doi-access = free }}</ref> Such an ancestor likely lived several hundred million years ago.<ref name="pmid24040233">{{cite journal | vauthors = Fiz-Palacios O, Romeralo M, Ahmadzadeh A, Weststrand S, Ahlberg PE, Baldauf S | title = Did terrestrial diversification of amoebas (amoebozoa) occur in synchrony with land plants? | journal =PLoS PLOS ONE | volume = 8 | issue = 9 | pages = e74374 | year = 2013 | pmid = 24040233 | pmc = 3770592 | doi = 10.1371/journal.pone.0074374 |url bibcode = 2013PLoSO...874374F | doi-access = free }}</ref> ''[[Dictyostelium discoideum]]'' and ''[[Polysphondylium pallidum]]'' are both capable of [[meiosis|meiotic]] [[sexual reproduction]] (see ''[[Dictyostelium discoideum#Sexual reproduction|''D. discoideum'' sexual reproduction]]'' and ''[[Polysphondylium pallidum#Sexual reproduction|''P. pallidum'' sexual reproduction]]''). Bloomfield<ref name=Bloomfield /> 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 (naturally occurring)|DNA damage]]. Such damage would make the induction of double-strand breaks by Spo11 redundant for the initiation of [[genetic recombination|recombination]] during meiosis, and thus explain its absence in this group.

== References ==