The diploid human genome has been estimated to contain 6 billion nucleotides. It is an enormous task for the proliferating cell to replicate the entire genome, due to the size and accuracy by which it must be accomplished. It must also be a very efficient process because the cell has a very limited time to finish the task. We are studying on the molecular level how DNA replication is accomplished in eukaryotic cells. There still remain many large questions that have not been completely resolved. It is not entirely known how DNA replication is initiated, or how a replication fork functions. We are focused on the proteins that participate at the eukaryotic replication fork. Our main focus lies on DNA polymerase epsilon that plays a role at the replication fork.
Our main goals are, (i) to understand how DNA polymerase epsilon interacts with other replication fork proteins, (ii) to understand how DNA polymerase epsilon participates at the replication fork and if DNA polymerase epsilon fulfills some other important function during the replication of the chromosomes, (iii) to understand how DNA polymerase epsilon contributes to the fidelity of the replication of the genome, (iv) to understand how DNA polymerase epsilon is involved in DNA repair processes and cell-cycle regulation. Our model system is S. cerevisiae and this allows us to complement our biochemical characterizations with yeast genetics in in vivo experiments.