Dynamic Organization of Chromatin Replication

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Maintaining the genetic information of the DNA is a dynamic interplay between chromosome territories and functional proteins targeted to characteristic nuclear domains. We investigate the interplay between chromosomal DNA and the replication machinery targeted to replication foci by high resolution time-lapse microscopy of living mammalian cells. This renewal application describes the results obtained during the first 1.5 years of the project. We could show for the first time that the changing patterns of replication foci during S-phase are not due to movements of foci through the nucleus. Individual replication foci assemble at a particular nuclear site, keep this position for a given period, and disassemble after finishing local DNA replication. Assembly and disassembly of different foci occurs asynchronously. Replication foci and replicated DNA move relatively to each other at given nuclear positions. We are currently testing whether these movements are due to a reeling of DNA through the replication factory. The results also suggest that replication foci contain hyperstructures able to replicate several individual subchromosomal foci. Future experiments will reveal whether this is due to a recognition of a defined spatio-/temporal track of subchromosomal foci by individual replication foci.