Publication: Evaluación de la expresión diferencial de hotspots de roturas de doble hebra de ADN y su regulación por la respuesta daño genómico en la meiosis de Saccharomyces cerevisiae
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2022-11-21
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Universidad Complutense de Madrid
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Abstract
Durante el proceso de meiosis dos divisiones celulares tienen lugar tras una sola ronda de replicación del material genético. En Saccharomyces cerevisiae, para que la meiosis ocurra de forma correcta, los cromosomas homólogos deben aparearse, hacer sinapsis y recombinar. La recombinación tiene su origen en roturas de doble hebra de ADN o DSBs (Double Strand Breaks) catalizadas por el complejo Spo11. Estas están reguladas espaciotemporalmente por las quinasas Mec1 y Tel11. Estas quinasas fosforilan residuos conocidos como (S/T)Q: serinas y treoninas que son seguidas en la secuencia aminoacídica por glutaminas. Se ha establecido que la fosforilación por parte de Tel1 de Rec114, uno de los componentes del complejo de Spo11, es capaz de inhibir la formación de DSBs. Cuando todos los residuos (S/T)Q de Rec114 son sustituidos por aminoácidos fosfomiméticos, se produce un retraso en la producción de DSBs. Este retraso conlleva una caída en la cantidad de DSBs cuando ocurre en fondos genéticos rad50S/sae2Δ. Este descenso es similar al que sucede en estas cepas al retrasar la producción de DSBs debido a un retraso en la replicación. Este no se produce, sin embargo, en fondos genéticos silvestres o en mutantes dmc1Δ, siendo la proteína Dmc1 una recombinasa meiótica. Se ha determinado también que la cantidad de hotspots descritos en fondos rad50S/sae2Δ es menor a la existente en un fondo dmc1Δ. Una posible causa para esto es que los hotspots que no están presentes en cepas rad50S/sae2Δ estén altamente regulados por Rec114. Por otro lado, esta regulación sería más laxa en los hotspots que si se expresan en esas condiciones...
During meiosis two cellular divisions are preceded by a single round of genome replication. In Saccharomyces cerevisiae, for meiosis to being correctly produced, homologous chromosomes must pair, synapse and recombine.Recombination has its origin in double strand breaks (DSBs) catalyzed by the Spo11 complex. They are spatiotemporally regulated by Mec1 and Tel1 kinases. These kinases phosphorylate residues known as (S/T)Q: serines and threonines followed by a glutamine in the aminoacidic sequence.It has been established that the phosphorylation by Tel1 of Rec114, one of the components of the Spo11 complex, leads to the inhibition of DSBs formation. When all the (S/T)Q residues of Rec114 are substituted by phosphomimetic aminoacids, a delay in the production of double strand breaks occur. This delay entails a reduction in the quantity of DSBs when it occurs in rad50S/sae2Δ genetics backgrounds. This reduction in DSBs is similar to the one seen when DSBs production is delayed by delaying DNA replication in rad50S/sae2Δ backgrounds. However, this reduction does not occur in wild type backgrounds or dmc1Δ, being the Dmc1 protein a meiotic recombinase.It has also been reported that the quantity of described hotspots in rad50S/sae2Δ backgrounds is lesser than the quantity of hotspots described in dmc1Δ backgrounds. One possible cause for this is that the hotspots that are not expressed in rad50S/sae2Δ strains may be highly regulated by Rec114. The rest of the hotspots, which are expressed under these conditions, would be less regulated by this protein...
During meiosis two cellular divisions are preceded by a single round of genome replication. In Saccharomyces cerevisiae, for meiosis to being correctly produced, homologous chromosomes must pair, synapse and recombine.Recombination has its origin in double strand breaks (DSBs) catalyzed by the Spo11 complex. They are spatiotemporally regulated by Mec1 and Tel1 kinases. These kinases phosphorylate residues known as (S/T)Q: serines and threonines followed by a glutamine in the aminoacidic sequence.It has been established that the phosphorylation by Tel1 of Rec114, one of the components of the Spo11 complex, leads to the inhibition of DSBs formation. When all the (S/T)Q residues of Rec114 are substituted by phosphomimetic aminoacids, a delay in the production of double strand breaks occur. This delay entails a reduction in the quantity of DSBs when it occurs in rad50S/sae2Δ genetics backgrounds. This reduction in DSBs is similar to the one seen when DSBs production is delayed by delaying DNA replication in rad50S/sae2Δ backgrounds. However, this reduction does not occur in wild type backgrounds or dmc1Δ, being the Dmc1 protein a meiotic recombinase.It has also been reported that the quantity of described hotspots in rad50S/sae2Δ backgrounds is lesser than the quantity of hotspots described in dmc1Δ backgrounds. One possible cause for this is that the hotspots that are not expressed in rad50S/sae2Δ strains may be highly regulated by Rec114. The rest of the hotspots, which are expressed under these conditions, would be less regulated by this protein...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 25-05-2022