The origin replication complex (ORC): The stone that kills two birds

✍ Scribed by Geneviève Almouzni

• Book ID: 101712629
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 491 KB
• Volume: 16
• Category: Article
• ISSN: 0265-9247
• DOI: 10.1002/bies.950160405

✦ Synopsis

The story began with the discovery of a protein complex present at replication origins in yeast('S2). This multiprotein complex known as ORC, for origin recognition complex, was purified on the basis of its properties to bind a yeast origin of replication, called ARS l(l). The hope was that this was the initiator protein activating eukaryotic replication origins. Nevertheless, being at the right place does not necessarily mean that you are doing the right job. Four recently published papers, however, together provide strong genetic evidence that ORC plays a role in replication initiati~n(~-~).

Remarkably, data presented in three of these paper^(^-^) are consistent with ORC acting in transcriptional silencing, a mode of repression of transcription seen at the two matingtype loci of S. cere~isiae(~). Thus ORC would function in both the processes of DNA replication and transcriptional silencing. Of course, the question is, how are these functions related?

Although the identity and structure of replication origins in higher eukaryotes are poorly understood, cis-acting sequences responsible for replication origins have been identified in yeast@). These sequences were able to confer autonomous replication to plasmids in which they were inserted, and were therefore named ARS, for autonomously replicating sequences. They were proved later to serve effectively as replication origins in plasmids. Furthermore, some of them also function as chromosomal replication origins@). The analyses of the sequences of ARS reveal that they contain two domains, A and B@). The A domain contains an ARS consensus sequence (ACS) of 11 base pairs [5'-