Regulation of MCM7 DNA Replication Licensing Activity

Miniature chromosome maintenance (MCM) proteins were initially identified from autonomously replicating sequence in Saccharomyces cerevisiae. Mutations of some of these proteins such as MCM7 or MCM3 in yeast result in loss of the large chunk of yeast chromosomes. MCM7 cDNA encodes a 543-amino acid protein and is ubiquitously expressed in all tissues. Initiation of DNA replication is a complex process involving the concerted action of many proteins. A large body of studies indicate that MCM7 is a critical component of DNA replication licensing complex in the yeast and xenopus (Chong et al., 1996; Coxon et al., 1992; Dalton and Whitbread, 1995; Kearsey et al., 1996). Some studies suggest that MCM4, 6 and 7 complex contains DNA helicase activity (Ishimi, 1997; You et al., 1999). DNA replication licensing complex is multimeric and phase specific. In the yeast, DNA replication licensing proteins such as MCM2-7 and several replication origin binding proteins such as Cdc6 and Cdt1 forms DNA replication licensing complex in G1 phase to enable DNA replication and to promote cell cycle entry into S phase. Such complex, however, dissipates in the S, G2 and M phases to prevent re-firing of DNA replication, and thus protect the integrity of genomes. There is little interest in MCM complex as target for oncongenic or tumor suppressor pathway until the links of MCM7 over-expression and amplification to several human malignancies were found (Brake et al., 2003; Honeycutt et al., 2006; Kan et al., 2009; Ren et al., 2006).