MCM3

Official Full Name

minichromosome maintenance complex component 3

Organism

Homo sapiens

GeneID

4172

Background

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein is a subunit of the protein complex that consists of MCM2-7. It has been shown to interact directly with MCM5/CDC46. This protein also interacts with and is acetylated by MCM3AP, a chromatin-associated acetyltransferase. The acetylation of this protein inhibits the initiation of DNA replication and cell cycle progression. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2018]

Synonyms

HCC5; P1.h; RLFB; P1-MCM3;

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Detailed Information

As an important member of the MCMs family, minichromo some maintenance 3 (MCM3) is closely related to the DNA replication process of organisms. The most studied species of MCM3 are saccharomyces cerevisiae and mammals. The study found that in S. cerevisiae, MCM3 is located on the left arm of chromosome 5, close to the centromere, and the nucleic acid sequence site in the Gene Bank is X53540. The MCM3 gene is 3924 bp long and contains an open reading frame (ORF) of approximately 3 kb. If translated from the first ATG, MCM3 encodes a protein of 971 amino acids with a molecular weight of 125 kDa at the amino terminus and carbon. There is a hydrophilic region at each end.

Figure 1. Regulation of the Minichromosome Maintenance Protein 3 (MCM3) Chromatin Binding by the Prolyl Isomerase Pin1.( Schumann, et al. 2018)

MCM3 has a defined nuclear localization sequence that has an early localization role for the aggregation of other MCM members. In brewer's yeast, MCM enters the nucleus at specific times during the cell cycle, and the nuclear membrane of the yeast does not rupture during mitosis. Studies have confirmed that MCM3 has nuclear localization sequestise (NLS), and there are four sites for phosphorylation of CDC28 near the sequence. Mutation of these sites revealed that it did not affect cell growth or activity, or affected the aggregation of MCM3.

Relationship Between MCM3 and Proliferating Cells

In addition to labeling proliferating cells, MCM3 can also label cells in quiescence; cells with proliferative potential or activity can be labeled without labeling the cells being differentiated. These unique markers make MCM3 to be an essential factor for cell proliferation. The mRNA of MCM3 can also have low levels of expression in cells in normal tissues, such as the small intestine, spleen, colon, and the like. The same is true for basal cells with proliferative potential in normal tissues, but the expression level is different from that in cancer cells, and the mechanism of action may be different.

Immunohistochemistry was used to detect MCM2, MCM 3, Ki-67, estrogen receptors and progesterone receptors in 23 normal endometrium, 9 intimal hyperplasia and 60 endometrial carcinoma tissues. In normal tissues, MCM3 in the proliferative phase was significantly higher than the secretory phase, which was consistent with the expression of Ki-67, and the same results were found in intimal hyperplasia tissues. However, MCM3 was significantly lower in the endometrial cancer tissue than in the proliferative phase, suggesting that MCM3 directly reflects cell proliferation in normal tissues and proliferating endometrium. When the cells become cancerous, the replication permit system is disordered, and the expression level of MCM3 is decreased.

MCM3 and Tumor

Due to the relationship between the MCM family and DNA replication, recent studies have examined the expression of MCMs in the tumor tissues, including MCM3, which indicates that MCM3 protein accurately reflects the proliferative activity of cells. According to its expression characteristics and marker index, it can better distinguish normal tissues, atypical hyperplasia tissues and tumor tissues, indicating that MCM3 is a reliable marker for precancerous, tumor diagnosis and prognosis. The study confirmed the overexpression of the MCM3 gene in several human cancers, including leukemia, lymphoma, and tumors of the cervix, colon, lung, stomach, kidney, and breast, as well as malignant melanoma. Western blot and immunohistochemistry revealed MCM3. Protein is detected to be elevated in most cancerous tissues.

References:

Arman, K. , Bozgeyik, E. , & Igci, Y. Z. . (2015). Review: mcm3 (minichromosome maintenance complex component 3).
Schumann, M. , Malešević, Miroslav, Hinze, E. , Mathea, S. , Meleshin, M. , & Schutkowski, M. , et al. (2018). Regulation of the minichromosome maintenance protein 3 (mcm3) chromatin binding by the prolyl isomerase pin1. Journal of Molecular Biology.
Yamamoto, K. , Makino, N. , Nagai, M. , Araki, H. , & Ushimaru, T. . (2018). Cdk phosphorylation regulates mcm3 degradation in budding yeast. Biochemical and Biophysical Research Communications.

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