Minichromosome maintenance complex and Cell division cycle 6 (MCM/CDC6)

The Minichromosome Maintenance (MCM) complex, specifically the MCM2-7 heterohexamer, and the Cell Division Cycle 6 (CDC6) protein are essential components of the eukaryotic DNA replication machinery [10, 12]. During the G1 phase of the cell cycle, CDC6 is recruited to the origin recognition complex (ORC) on DNA, where it acts as a molecular loader to facilitate the assembly of the MCM2-7 complex onto chromatin, a process known as "replication licensing" [10, 11]. This assembly forms the pre-replicative complex (pre-RC), which is a prerequisite for DNA unwinding and the initiation of DNA synthesis in the S phase [3, 9]. Because these proteins are highly expressed in rapidly proliferating cancer cells but absent in quiescent or differentiated cells, they serve as critical biomarkers for malignancy and attractive targets for anti-cancer therapy [1, 3, 13]. Small molecules and inhibitors targeting the helicase activity of the MCM complex or the stability of CDC6, such as Simurosertib and NSC-95397, are being explored to induce cell cycle arrest and apoptosis in tumors [4, 7, 8]. Furthermore, the deregulation of these factors is linked to genomic instability and various carcinomas, making them focal points for precision oncology [5, 16].

Other names

MCM2-7 complexCDC6Pre-replicative complex componentsDNA replication licensing factorsRLF

Inhibition of DNA replication initiation by preventing the assembly of the pre-replicative complex, inducing CDC6 degradation, or inhibiting the helicase activity of the MCM2-7 complex to block DNA unwinding.