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Bladder cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Robert Huddart, Alan Horwich, Pradeep Kumar
Recently, there has been much interest in the development of methods to detect proteins of the minichromosome maintenance (MCM) family, which are known to play a critical regulatory role in the initiation of DNA replication. It has previously been demonstrated that deregulated expression of MCM proteins is characteristic of epithelial-cell carcinogenesis, resulting in the exfoliation of MCM-positive tumour cells that have been used in the screening of cervical carcinoma.72 Because MCM proteins identify both proliferating and non-proliferating cells with proliferative potential, MCM protein expression is a more sensitive marker of epithelial carcinogenesis than the expression of conventional proliferation markers. The percentage of MCM5-expressing cells in urothelial carcinoma is related to the grade of TCC, averaging 78% for poorly differentiated, 70% for moderately differentiated and 45% for well-differentiated tumours.73 Subsequent investigation has demonstrated that elevated levels of MCM5 in urine sediments are highly predictive of bladder cancer,74 raising the possibility that this technique could be used in primary staging, detection of relapse and screening for bladder cancer.
Introduction to Molecular Biology
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Although knowledge of the structure of the replication machinery in eukaryotes is still limited due to its complexity, there are many similarities with the simpler prokaryotes DNA replication process. In eukaryotic cells, DNA exists in the nucleus as a very compact and condensed structure. In order to begin the replication process, this structure must be opened up, so the DNA polymerase enzyme can copy the DNA template. The replication process takes place at a specific site called origin of replication, which is rich in AT content. The first step in DNA replication begins with the binding of the origin recognition complex (ORC) to the origin of replication. ORC complex is a hexamer of related proteins that function as a replication initiation factor that promotes the unwinding or denaturation of DNA. Following the binding of the ORC complex, other proteins (Cdc6/Cdc18 and Cdt1) will bind and coordinate the recruitment of the minichromosome maintenance function (MCM) complex to the origin of replication. The MCM complex is a hexamer and is thought to be the major DNA helicase in eukaryotic organisms. Once the binding of MCM occurs, a fully licensed pre-initiation replication complex (pre-RC) now exists. This process occurs during the G1 phase of the cell cycle and therefore, cannot initiate the replication. Replication only occurs during the S phase. Thus, separating the licensing and activation is a mechanism that ensures only one replication per origin in a cell cycle.
Genetics of mammalian meiosis
Published in C. Yan Cheng, Spermatogenesis, 2018
Formation of DSBs entails a DNA damage response, leading to phosphorylation of histone H2AX by ATM.65,66 Following generation of DSBs, SPO11 is covalently attached to the 5’ strands of both ends of the DSB. DSB breaks undergo end resection to produce 3’ single-stranded DNA (ssDNA) ends, releasing SPO11-oligonucleotide complexes.67 RPA, an ssDNA-binding complex, coats the ssDNA to protect it from degradation and prevent secondary structure formation.68 RAD51 and DMC1 are also ssDNA-binding proteins and exhibit recombinase activities. RAD51/DMC1 recombinase is loaded onto ssDNA, displaces RPA, and directs strand invasion into the duplex of the homologous chromosomes, resulting in the formation of displacement loop (D-loop).69 DMC1 is a meiosis-specific paralogue of RAD51.70 DMC1 favors repair of meiotic DSBs through a nonsister chromatid rather than a sister chromatid. The MND1/HOP2 heterodimer interacts with RAD51/DMC1 and stimulates their recombinase activity to generate the D-loop recombination intermediates.71 MCMDC2, a member of the minichromosome maintenance (MCM) helicase family, is required for RAD51- and DMC1-directed strand invasion or stabilization of recombination intermediates.72,73 MEIOB is a meiosis-specific ssDNA-binding protein.74,75 MEIOB interacts and forms a heterodimer with SPATA22, which is also a meiosis-specific protein.74,76 The MEIOB/SPATA22 complex interacts with the RPA complex and localizes to DSB sites.77 The MEIOB/SPATA22 complex has been hypothesized to function in the second end capture and maintenance of RAD51 foci.74,78 Second end capture results in the formation of the recombination intermediate–double Holliday junction (dHJ). Most proteins involved in meiotic DSB repair form foci at the DSB sites on meiotic chromosomes. Since meiotic recombination occurs in both male and female germ cells, loss of any of these recombination-related proteins leads to meiotic arrest and thus sterility in both sexes.
Mutational analysis of minichromosome maintenance complex component (MCM) family genes in Chinese Han women with polycystic ovarian syndrome
Published in Gynecological Endocrinology, 2023
Jiangyan Zhou, Faying Liu, Lifeng Tian, Ming Yang, Jun Tan, Xianxian Liu, Peishuang Li, Jia Chen, Ge Chen, Lixian Xu, Lisha Peng, Qiongfang Wu, Yang Zou
The minichromosome maintenance (MCM) family is highly conserved in vertebrates and comprises MCM2 through MCM10. These proteins play essential roles in DNA replication and cell cycle progression. Indeed, MCM proteins not only interact with S-phase checkpoint regulators, but also with components of DNA repair pathway [14–16]. The MCM 2-7 complex is instrumental for cell-cycle control, an operation that occurs during the G1 and G2 phases of mitosis [14,15]. MCM8 complexes with MCM9 and has a role in DNA repair and genome instability [17–19]. MCM10 involves in DNA replication and chromosomal instability [16,20]. Recently, studies showed that dysfunctional mutations in MCM8 and MCM9 could lead to premature ovarian failure (POF) and primary ovarian insufficiency (POI) [19,21–23]. Considering the shared biological features between POF/POI and PCOS, such as dysregulation of steroid hormones, and ovarian dysfunction, moreover, some mutations in POF/POI also exist in PCOS, such as AMH, FSHR, GDF9, and BMP15 [24–26], thus, we speculate that mutations/rare variants of MCMs might exist in Chinese patients with PCOS.
Establishment of the prediction model and biological mechanism exploration for secondary imatinib-resistant in gastrointestinal stromal tumor
Published in Scandinavian Journal of Gastroenterology, 2022
Chao Wang, Zhanlong Shen, Kewei Jiang, Zhidong Gao, Yingjiang Ye
We found most of the 44 DEGs biologically enriched in DNA replication, which is the frequent cellular process that can lead to genome instability [25]. The minichromosome maintenance protein complex is composed of six proteins (MCM2-7) and is a key player in the initiation of DNA replication [26]. Shim et al. evaluated MCM6 expression in 211 GIST samples and found high MCM6 expression was associated with tumor size, mitosis, tumor necrosis, presence of recurrence/metastasis, and poor overall survival [27]. AXL is involved in the cell cycle, which expression was strong in KIT-negative GIST samples, and knockdown of AXL inhibited viability in KIT-negative GIST cell lines [28]. Sugase et al. found inhibition of the FAK signaling showed an inhibitory effect on cell growth and suppressed the phosphorylation of AKT, indicating a cross-talk between the AKT and FAK pathways in the secondary imatinib-resistant GIST cells [29].
MCM7 affects the cisplatin resistance of liver cancer cells and the development of liver cancer by regulating the PI3K/Akt signaling pathway
Published in Immunopharmacology and Immunotoxicology, 2022
It has already been reported that the abnormal expression of the minichromosome maintenance (MCM) complex, which is present in various human tumors, is related to the poor prognosis of cancer patients [5,6]. Minichromosome maintenance protein 7 (MCM7), a critical member of the MCM complex, is not expressed or poorly expressed in normal tissues, but is overexpressed in multiple malignancies [7,8]. Kim et al. proposed that up-regulation of MCM7 plays a unique role in cisplatin (DDP) resistance in bladder cancer patients [9]. Therefore, the present study is focused on investigating the effect of MCM7 on cell proliferation and apoptosis, as well as the resistance of liver cancer cells to cisplatin, with the hope of providing information regarding the pathogenesis and clinical treatment of liver cancer.