2 research outputs found
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
Prebi贸ticos y su efecto en la biod sponibilidad del calcio Prebiotics and their effect on calcium bioavailability
En la b煤squeda de medidas de prevenci贸n de enfermedades cr贸nicas no trasmisibles, se piensa en los prebi贸ticos como una forma efectiva, saludable y relativamente barata para la optimizaci贸n de la absorci贸n de Ca. El aumento de la expectativa de vida de la poblaci贸n y el incremento de enfermedades como la osteoporosis traen graves consecuencias a la salud del individuo, acarreando importantes desembolsos econ贸micos. En esta revisi贸n se condensa el conocimiento presente sobre el efecto fisiol贸gico del consumo de carbohidratos prebi贸ticos y su posible interferencia en la biodisponibilidad del Ca, como tambi茅n las posibilidades de su empleo en estrategias para combatir las deficiencias del mineral. Se elabor贸 una recopilaci贸n de los estudios originales realizados con mayor impacto en el tema, dando preferencia a los publicados en los 煤ltimos 6 a帽os. Utilizamos las bases de datos PubMed, Lilacs e SciELO, usando las palabras claves calcio, prebi贸ticos e probi贸ticos.<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