A top-down view on DNA replication and recombination from 9,000 feet above sea level

The triennial Keystone Symposium on 'DNA Replication and Recombination' brought together researchers working on various aspects of genome duplication, recombination and repair. A clear trend of this exciting meeting was a further shift from 'ovals and arrows' models to a more mechanistic understanding of the processes underlying DNA replication and recombination. This shift has been made possible in part by a growing number of solved protein structures, often in complex with DNA, and elegant single-molecule approaches. Several of the presentations revealed an intimate link between DNA replication and DNA recombination, bringing these two fields closer together than ever. Here we report a few of the highlights of the meeting.The MCM2-7 protein complex is the precursor of the replicative helicase that unwinds DNA in front of the active replication complex. During the G1 phase of the cell cycle, the helicase is loaded in an inactive form onto DNA. In S phase, MCM2-7 is activated by the cyclin-dependent and Dbf4-dependent kinases to become a processive replicative helicase. This activation requires the assembly of a large number of replication factors, culminating in the formation of the Cdc45-GINS-MCM2-7 (CMG) complex, which has strong helicase activity in vitro. Michael Botchan (University of California, Berkeley, USA) presented three-dimensional electron microscopy structures of the entire Drosophila melanogaster CMG complex. Interestingly, Cdc45 and GINS bridge a weak interface between Mcm2 and Mcm5, potentially sealing a gap between the two subunits. Using mutational data and structural information, Botchan suggested that the leading strand of the DNA passes through the central channel of the CMG complex. Data presented by Johannes Walter (Harvard Medical School, Boston, USA) also suggest that CMG operates by steric exclusion, with only the leading strand passing through the central channel of the complex. Thus, the two labs agree that the model in which the double