Two recent papers have for the first time given us an opportunity to glimpse the protein-DNA complexes present at eukaryotic origins of DNA replication. The first of these papers, by Bell and Stillman('), describes the purification from yeast cells of a multiprotein complex, ORC (standing for 'Origin Recognition Complex'), that binds with great sequence specificity to a yeast origin of DNA replication, called ARS1. There is a striking correlation between the ability of the ORC complex to bind specific DNA sequences and the ability of these sequences to function as origins or replication. The second paper, from Diffley and uses genomic footprinting to investigate proteins normally bound to ARSl in the yeast cell. The genomic footprint observed over this region corresponds almost exactly to the footprint that ORC inakes in vitru. Not only does this strongly imply the binding of ORC to origins of replication in vivo, it also suggests that ORC binds these origins throughout most, if not all, of the cell division cycle. To replicate their large genomes, eukaryotic cells initiate pairs of replication forks at between 1000 to 10000 di 1Terent sites scattered throughout the chromosomal DNA. Although the identity and structure of replication origins in higher eukaryotes is not at all well understood, the situation in yeast is clearer: and many yeast origins of replication have been identified as relatively small DNA scquence elements. Originally this identification was through a transformation assay for sections of genomic DNA that could support the autonomous replication in yeast of extrachromosomal DNA molecules carrying them. Subsequent development of 2-D gel techniques showed that thesc Autonomously Replicating Sequences (ARSs) actually were sites at which DNA replication initi~ited(~-~). Analysis of the structure of ARSs revealed that they consist of a highly conserved core consensus (or

'A') element of 1lbp long, 5'-T~TTTA'L'cAcTn"~-3', flanked on its 3' side by a larger and less-well conserved 'B' region, usually