THE MULTIDOMAIN STRUCTURE OF ORC1P REVEALS SIMILARITY TO REGULATORS OF DNA-REPLICATION AND TRANSCRIPTIONAL SILENCING

The origin recognition complex (ORC) is a six protein assembly that bi nds S. cerevisiae origins of replication and directs DNA replication t hroughout the genome and transcriptional silencing at the yeast mating -type loci. Here we report the cloning of the genes encoding the 120 k Da (ORC1), 62 kDa (ORC3), and 56 kDa (ORC4) subunits of ORC and the re constitution of the complete complex after expression of all six subun its in insect cells. Orc1p is related to Cdc6p and Cdc18p, which regul ate DNA replication and mitosis, and to Sir3p, a regulator of transcri ptional silencing. The N-terminal region of Orc1p is highly related to Sir3p, and studies of Orc1p/Sir3p chimeric proteins indicate that thi s domain is dedicated to the transcriptional silencing function of ORC .