Identification and characterization of MmORC4 and MmORC5, two subunits of the mouse origin of replication recognition complex

Two new members of the mouse origin recognition complex (ORC) have been clo ned that are closely related to Saccharomyces cerevisiae ORC4 and ORC5 as w ell as to their human homolog. Both MmORC4p and MmORC5p have a putative nuc leotide triphosphate binding motif. Transcription of MmORC4 and MmORC5 is n ot suppressed in mouse NIH3T3 fibroblasts made quiescent by serum starvatio n. The transcription levels of both ORC genes are constantly high in all ph ases of the cell cycle. A screen based on the two-hybrid approach suggests that the product of the ORC4 gene interacts with the ORC2, but not with the ORC1 protein. The conservation of structure among members of the ORC4- and ORC5-related family of proteins suggests that these proteins play a key ro le in the initiation of DNA replication in all eukaryotes.