Circles in the sand.

Introduction F. Jacob (Paris, France), co-creator of the replicon hypothesis and the operon model, opened the workshop with his memories of a summer 40 years ago. In the early morning, he and Sydney Brenner would accompany their eight children to the beach so that the ladies of the two families could sleep. As the two men talked, they illustrated their thoughts by drawing models in the sand. The issues were how the replication of DNA could be regulated and coupled to cell growth—problems that are still largely unsolved. They reasoned that, because of its extreme precision and specificity, replication could not be regulated merely by the pool of available precursors. They postulated that autonomous replication of a bacterial plasmid or a chromosome might be governed by a cis-acting sequence, the replicator, present on each DNA molecule, and a gene encoding a trans-acting initiator protein that could bind specifically to the replicator. These two elements would constitute a replication unit, the replicon, that could ensure the regulated duplication of the DNA contiguous with the replicator (Fig.1; Jacob et al., 1963). Four decades later, the replicon model continues to provide a fruitful framework for the exploration of increasingly complex cisand trans-acting regulatory elements, and these were a main focus of the workshop. Other topics of interest were the relationship between replication and genomic stability, and the links between the replication and segregation of daughter chromosomes. Some of the most exciting new work presented at the meeting is discussed in this report.