A novel role of small RNA pathways in regulating DNA replication in polyploid ce...
Small RNA-mediated gene regulation and DNA replication are fundamental genome-regulatory pathways essential for cellular life, organismal development, and disease prevention. While small RNA pathways are known to sequence-specific...
Small RNA-mediated gene regulation and DNA replication are fundamental genome-regulatory pathways essential for cellular life, organismal development, and disease prevention. While small RNA pathways are known to sequence-specifically regulate DNA copy number in some unicellular animals, such connections have yet to be found in multicellular animals. With this project, I will investigate and mechanistically characterize such a potential connection in the Drosophila animal model system. Piwi-interacting RNAs (piRNAs), a class of animal small RNAs, safeguard the germline genome against repetitive DNA proliferation by guiding repressive heterochromatin formation at target loci. In Drosophila melanogaster ovarian nurse cells, heterochromatic (peri)centromeric DNA repeats undergo selective local suppression of DNA replication thus lowering their relative copy number. Interestingly, abundant piRNAs able to target to these 'underreplicated' regions have been found, yet the potential functional interactions between small RNA genome defense and DNA replication remain unexplored. With this project, I will bridge this gap by investigating the role of satellite piRNAs in Drosophila melanogaster, focusing on the interplay between regulated DNA replication and small RNA genome defense. Two interconnected hypotheses will be examined: (1) piRNA-directed heterochromatin formation regulates centromeric DNA copy number, and (2) piRNA-regulated heterochromatin sinks alter epigenetic inheritance. To do so, I will apply advanced sequencing- and imaging-based methods for DNA copy number quantification and leverage the powerful Drosophila genetics to uncover underlying molecular mechanisms.In sum, my investigation of small RNA-based regulation of DNA replication holds the promise to reveal a new paradigm in animal genome regulation and to provide deeper insights into the mechanisms regulating genome stability and the role of piRNAs in maintaining it.ver más
Seleccionando "Aceptar todas las cookies" acepta el uso de cookies para ayudarnos a brindarle una mejor experiencia de usuario y para analizar el uso del sitio web. Al hacer clic en "Ajustar tus preferencias" puede elegir qué cookies permitir. Solo las cookies esenciales son necesarias para el correcto funcionamiento de nuestro sitio web y no se pueden rechazar.
Cookie settings
Nuestro sitio web almacena cuatro tipos de cookies. En cualquier momento puede elegir qué cookies acepta y cuáles rechaza. Puede obtener más información sobre qué son las cookies y qué tipos de cookies almacenamos en nuestra Política de cookies.
Son necesarias por razones técnicas. Sin ellas, este sitio web podría no funcionar correctamente.
Son necesarias para una funcionalidad específica en el sitio web. Sin ellos, algunas características pueden estar deshabilitadas.
Nos permite analizar el uso del sitio web y mejorar la experiencia del visitante.
Nos permite personalizar su experiencia y enviarle contenido y ofertas relevantes, en este sitio web y en otros sitios web.