Studies on the Initiation Stage

We have cloned ORC from multiple sources, including S. pombe (Sp), human (h) and S. cerevisiae (Sc). The properties of these complexes differ as do their interactions with DNA. The SpORC and ScORC contain stoichiometric levels of six distinct subunits while hORC contains near stoichiometric levels of ORC 1-5 subunits but only low levels of the ORC6 subunit.

Studies on Elongation Stage

Three different DNA polymerases (a, d and e) are involved in supporting DNA replication in all eukaryotes. DNA polymerase a is associated with DNA primase which catalyzes the formation of short oligoribonucleotides on both leading and lagging DNA strands that are elongated for only a short length by DNA polymerase a.

Studies with Alternative Clamp Loader Derivatives

The five subunit complex RFC loads PCNA onto DNA and is essential for replication. Recently, multiple derivatives of RFC (the replicative clamp loader) have been isolated and shown to play specific roles in DNA transactions. A five subunit complex in which the large subunit of RFC (RFC1) is replaced by Rad17 (Rad17-RFC) is involved in DNA damage response and replication check-point control.