Abstract
The MCM complex controls the once per cell cycle DNA replication in eukaryotic cells. In a process known as DNA replication licensing, it primes chromatin for DNA replication by binding origins of DNA replication during the late M to early G1 phase of the cell cycle. Activated by S phase promoting protein kinases, the origin-bound MCM complexes unwind the double stranded DNA at the origins, recruit DNA polymerases and initiate DNA synthesis. Coupled with the initiation of DNA replication in the S phase, the MCM complexes move away from replication origins as a component of the DNA replication fork, likely serving as DNA helicases. Their departure deprives replication origins the ability to re-initiate DNA replication for the reminder of the cell cycle. Because of its vital role in genome duplication in proliferating cells, deregulation of the MCM function results in chromosomal defects that may contribute to tumorigenesis. The MCM proteins are highly expressed in malignant human cancers cells and pre-cancerous cells undergoing malignant transformation. They are not expressed in differentiated somatic cells that have been withdrawn from the cell cycle. Therefore, these proteins are ideal diagnostic markers for cancer and promising targets for anticancer drug development. In this article, I will overview the structures and functions of the MCM complex with an effort to integrate insights from recent biochemical and structural studies. Discussions will also cover activities and structures of the complex that may be useful for the development of drug screens.
Keywords: dna replication, mcm complex, replication licensing, dna helicase
Current Cancer Drug Targets
Title: The MCM Complex: Its Role in DNA Replication and Implications for Cancer Therapy
Volume: 5 Issue: 5
Author(s): Ming Lei
Affiliation:
Keywords: dna replication, mcm complex, replication licensing, dna helicase
Abstract: The MCM complex controls the once per cell cycle DNA replication in eukaryotic cells. In a process known as DNA replication licensing, it primes chromatin for DNA replication by binding origins of DNA replication during the late M to early G1 phase of the cell cycle. Activated by S phase promoting protein kinases, the origin-bound MCM complexes unwind the double stranded DNA at the origins, recruit DNA polymerases and initiate DNA synthesis. Coupled with the initiation of DNA replication in the S phase, the MCM complexes move away from replication origins as a component of the DNA replication fork, likely serving as DNA helicases. Their departure deprives replication origins the ability to re-initiate DNA replication for the reminder of the cell cycle. Because of its vital role in genome duplication in proliferating cells, deregulation of the MCM function results in chromosomal defects that may contribute to tumorigenesis. The MCM proteins are highly expressed in malignant human cancers cells and pre-cancerous cells undergoing malignant transformation. They are not expressed in differentiated somatic cells that have been withdrawn from the cell cycle. Therefore, these proteins are ideal diagnostic markers for cancer and promising targets for anticancer drug development. In this article, I will overview the structures and functions of the MCM complex with an effort to integrate insights from recent biochemical and structural studies. Discussions will also cover activities and structures of the complex that may be useful for the development of drug screens.
Export Options
About this article
Cite this article as:
Lei Ming, The MCM Complex: Its Role in DNA Replication and Implications for Cancer Therapy, Current Cancer Drug Targets 2005; 5 (5) . https://dx.doi.org/10.2174/1568009054629654
DOI https://dx.doi.org/10.2174/1568009054629654 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Characterization of Breast Lesions by Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS)
Current Medical Imaging Overview of the Structure and Function of Protein Kinases
Current Enzyme Inhibition Anti-angiogenic Treatment in Metastatic Colorectal Cancer: Current Issues and Future Aims
Current Cancer Therapy Reviews An Overview on Fibroblast Growth Factors: Structural, Functional and Therapeutic Implications
Current Proteomics Current Status of Epigenetics and Anticancer Drug Discovery
Anti-Cancer Agents in Medicinal Chemistry Physical and Chemical Stimuli-Responsive Drug Delivery Systems: Targeted Delivery and Main Routes of Administration
Current Pharmaceutical Design Left-Right Asymmetry in Embryonic Development and Breast Cancer: Common Molecular Determinants?
Current Medicinal Chemistry Channel-Like Functions of the 18-kDa Translocator Protein (TSPO): Regulation of Apoptosis and Steroidogenesis as Part of the Host-Defense Response
Current Pharmaceutical Design Zebrafish: Predictive Model for Targeted Cancer Therapeutics from Nature
Current Cancer Drug Targets Influence of Polymer Molecular Weight on in-vitro Characteristics and Cytotoxicity of Fulvestrant Loaded Nanoparticles
Current Drug Therapy Overview of SLC22A and SLCO Families of Drug Uptake Transporters in the Context of Cancer Treatments
Current Drug Metabolism Recent Advances in Biological Strategies for Targeted Drug Delivery
Cardiovascular & Hematological Disorders-Drug Targets Carbon Nanotubes as an Advanced Drug and Gene Delivery Nanosystem
Current Nanoscience Indoleamine 2,3-Dioxygenase, an Emerging Target for Anti-Cancer Therapy
Current Cancer Drug Targets HR MAS MR Spectroscopy in Metabolic Characterization of Cancer
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Novel Peptide-Based Scaffolds for Drug Discovery (Executive Guest Editor: Julio A. Camarero)]
Current Pharmaceutical Design Receptor Tyrosine Kinases are Signaling Intermediates of G Protein- Coupled Receptors
Current Pharmaceutical Design Ligand Conjugated Targeted Nanotherapeutics for Treatment of Neurological Disorders
Current Pharmaceutical Design Triazole and Oxadiazole Containing Natural Products: A Review
The Natural Products Journal Radiolabelled Probes Targeting Tumor Hypoxia for Personalized Medicine
Current Pharmaceutical Design