Discovering the structural and mechanistic principles of human helicase-loading control and its misregulation in cancer

In cancer, the regulation of DNA replication is altered, resulting in genomic instability. Here we aim to understand the foundations of DNA replication regulation by studying how replication factors assemble on human DNA replication origins. Recently we have reconstituted human helicase loading using purified proteins (see picture below). Currently, we use this system to identify the minimal set of proteins required for complex assembly, its assembly process, the structure of critical intermediates and the influence of cancer-associated mutations on human helicase loading. Moreover, we want to understand how human DNA replication origins are specified and how helicase loading is regulated.

If you are interested in the biochemical analysis of human helicase loading, please contact us; we have an open postdoctoral position in this area.

Establishment of the human pre-RC assay
Figure 1. Establishment of the human pre-RC assay