LMS WIP Seminar – Max Reuter
“Functional analysis of the MCM2-7 helicase activation during DNA replication initiation”
Precise DNA replication is essential for all living cells. Thus, eukaryotic cells have evolved a sophisticated system for replicating DNA. First, the replicative helicase, MCM2-7, is assembled as a hexameric ring around double-stranded origin DNA, resulting in helicase loading at DNA replication origins. Second, the MCM2-7 complex undergoes remodelling and eventually becomes activated in early S-phase via a poorly understood process Third, the replisome travels along the genome synthesising new DNA.
Exploiting an exclusively available, chemical-biology approach to control MCM2-7 ring opening, we characterise the molecular events that take place during the replicative helicase activation process. Together with Next Generation Sequencing methods we are now able to explore this remodelling process in vivo at near base pair resolution. Identification of the underlying mechanisms in helicase activation may answer longstanding questions in the field of DNA replication and provide novel targets for cancer drug development.
DNA Replication group