Epigenetic marks such as histone methylation help to define how the DNA code is read. Alterations in this process can result in altered gene expression, a loss of cellular identity and cancer. To preserve expression patterns, epigenetic information must be correctly maintained. Thus, during the copying of the DNA strands that occurs before cell division, epigenetic marks must be transmitted to the new DNA strands. There are indications from cellular models that the machinery which duplicates DNA also participates in the transmission of epigenetic information. However, the replisome, the ensemble of proteins that participate in DNA replication, has not been characterised in a higher organism such as the roundworm C. elegans. In this project, we probed whether mutations in C. elegans replication components alter the transmission of epigenetic information. First, we used a fluorescent reporter assay to characterise interactions between replisome components in collaboration with another lab. Secondly, we tested the replisome mutants for fertility defects over generations, a phenotype that is associated with alterations in epigenetic transmission. Both approaches yielded novel insights into the function of the replisome, such as new genetic interactions that have not been reported to date. In addition, we found that combined loss of two non-essential factors increases gene expression, in regions that are normally repressed. We have indications that this increased expression in the double mutant is due to a loss of repressive histone marks. Furthermore, the double mutant exhibits a loss of fertility over generation which is reversible, and which can be repressed by downregulation of a histone demethylase. Our work describes for the first time the interplay of these two DNA replication factors and its effects on the transmission of epigenetic information.
