TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function

Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that repairs 'abortive' TOP2-induced DSBs, in individuals with intellectual disability, seizures and ataxia. We show that cells from affected individuals are hypersensitive to TOP2-induced DSBs and that loss of TDP2 inhibits TOP2-dependent gene transcription in cultured human cells and in mouse post-mitotic neurons following abortive TOP2 activity. Notably, TDP2 is also required for normal levels of many gene transcripts in developing mouse brain, including numerous gene transcripts associated with neurological function and/or disease, and for normal interneuron density in mouse cerebellum. Collectively, these data implicate chromosome breakage by TOP2 as an endogenous threat to gene transcription and to normal neuronal development and maintenance

Prebióticos y su efecto en la biod sponibilidad del calcio Prebiotics and their effect on calcium bioavailability

En la búsqueda de medidas de prevención de enfermedades crónicas no trasmisibles, se piensa en los prebióticos como una forma efectiva, saludable y relativamente barata para la optimización de la absorción de Ca. El aumento de la expectativa de vida de la población y el incremento de enfermedades como la osteoporosis traen graves consecuencias a la salud del individuo, acarreando importantes desembolsos económicos. En esta revisión se condensa el conocimiento presente sobre el efecto fisiológico del consumo de carbohidratos prebióticos y su posible interferencia en la biodisponibilidad del Ca, como también las posibilidades de su empleo en estrategias para combatir las deficiencias del mineral. Se elaboró una recopilación de los estudios originales realizados con mayor impacto en el tema, dando preferencia a los publicados en los últimos 6 años. Utilizamos las bases de datos PubMed, Lilacs e SciELO, usando las palabras claves calcio, prebióticos e probióticos.<br>The increased life expectancy and prevalence of non-communicable chronic diseases have serious health and economic consequences on the population. Among the useful tools for preventing osteoporosis, prebiotics are thought to be an effective, healthy and relatively cheap way of optimizing calcium absorption. The objective of this review was to summarize the present knowledge on the physiological effects of prebiotic carbohydrate consumption and its possible interference with calcium bioavailability. The possibility of using prebiotics to fight calcium deficiency was also assessed. The keywords calcium, prebiotics and probiotics were used to search the PubMed, Lilacs and SciELO databases for the most significant original studies on the subject published in the last 6 years