TEI · Development of a model system to study the role of chromatin factors during transgenerational epigenetic inheritance (TEI) in C. elegans

Development of a model system to study the role of chromatin factors during transgenerational epigenetic inheritance (TEI) in C. elegans

The main purpose of the project was to study the biochemistry of a single locus in the C. elegans genome and discover novel pathways in gene silencing and transgenerational epigenetic inheritance (TEI). So far, we have established a unique technology for the first time in C. elegans and discovered a new pathway that silences selfish elements such as transposons. Unexpectedly, this new pathway functions independent of the germline piRNA pathway and comprises poly-ADP polymerases (PARPs), which are very well studied for DNA damage recognition in humans and mice. Here as a result of our project, we propose a new pathway in C. elegans that uses DNA damage as a signal on transposons for silencing machinery independently of small RNA pathways. As a concept, DNA damage is used as a signal for non-self recognition as well as a defence mechanism in bacterial CRISPR and paramecium DNA elimination mechanisms. Further experiments in this project will detail the mechanistic aspects of this new pathway. One component of this new pathway is an uncharacterised protein with a catalytically dead PARP (poly-ADP polymerase) domain. This finding is crucial since PARP enzymes are important targets in breast and ovarian cancer patients. Further understanding of PARP enzyme regulation and inhibition in C. elegans might have potential therapeutic applications for patients with breast and ovarian cancer. What is more, a potential role for PARP enzymes has been reported in immunological and neurobiological disorders. Our discovery do not just have a potential for a therapeutic application for cancer, but also an additional understanding in neurobiological and immunological disorders.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз