LMS Remote Seminar – Julian Blow
‘New Pathways for Completing the Replication of Human-Sized Genomes’.
In order to prevent re-replication of DNA in a single cell cycle, eukaryotic cells license replication origins for use by the loading of MCM2-7 complexes only in late mitosis and G1. However, if two converging replication forks irreversibly stall – a ‘double fork stall’ (DFS) – the DNA in between cannot be replicated by conventional means. Mathematical analysis of DFSs can explain origin distribution in yeasts but predicts that DFSs are highly likely in animal cells because of their large genomes.
In transcriptionally quiescent Xenopus early embryos, we show that the number of licensed origins is extremely high: on average one Mcm2-7 double hexamer every 2-300 bp. We show that this high density of origins can reduce the probability of double fork stalls to levels compatible with overall early embryo survival. Theoretical analysis sets an upper limit of ~3 tera-base pairs (a universal replication constant) on genomes replicating by this simple scheme.