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.