Connecting ORC and heterochromatin: why?

Considerable evidence connects heterochromatin or silenced chromatin with the Origin Recognition Complex (ORC) which is needed for initiation of DNA replication. In this review we consider biological forces that might be served by this connection. The prevailing view in the literature is that ORC recruits heterochromatin. This seems paradoxical because a replication initiator, ORC, would be recruiting factors which seem to oppose replication by forming inaccessible chromatin structures. Here we suggest a different view, that heterochromatin recruits ORC to facilitate replication of hard-to-replicate heterochromatic regions. We consider how existing data can be reconciled with this viewpoint, and we consider the biological predictions that arise from this perspective