Minichromosome maintenance protein (MCM) (MCM)

Minichromosome maintenance (MCM) proteins, specifically the MCM2-7 complex, are essential components of the eukaryotic DNA replication machinery. They function as a heterohexameric helicase that unwinds the DNA double helix at replication origins and moves with the replication fork during elongation [1, 14, 19]. MCM proteins are loaded onto chromatin during the late M to early G1 phase in a process called 'licensing,' ensuring that the genome is replicated only once per cell cycle [11, 19]. Beyond replication, they play roles in the DNA damage response, chromatin remodeling, and transcription regulation [2, 8, 12, 18]. In many cancers, MCM proteins are significantly overexpressed, making them valuable biomarkers for cell proliferation and poor prognosis [3, 15, 16]. Because cancer cells are highly dependent on efficient DNA replication, the MCM complex has emerged as a promising therapeutic target. Experimental inhibitors and certain existing drugs, such as ciprofloxacin, have been shown to inhibit MCM helicase activity, leading to replication stress, DNA damage, and apoptosis in malignant cells [4, 13, 16]. Other approaches include the development of small-molecule MCM7 inhibitors and degraders like AS4583 [13, 16]. However, the high surplus of MCM proteins in cells, known as the 'MCM paradox,' presents a challenge for achieving complete therapeutic inhibition, as only a small fraction of loaded MCMs is required for normal replication [23]. Additionally, targeting these proteins carries risks of toxicity to healthy proliferating tissues and potential genomic instability [13, 16].

Other names

MCM complexMCM2-7 complexDNA replication licensing factorReplicative helicaseMCM family

Inhibition of DNA helicase activity, disruption of pre-replication complex assembly, and induction of replication stress leading to apoptosis.