Introduction to Molecular Biology
Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman in Molecular Imaging in Oncology, 2008
DNA replication is the process of copying double-stranded DNA molecules and it takes place during the S phase of cell cycle for eukaryotes. This process is extremely important for all living organisms. The fidelity of DNA replication is astounding, with an average of only one mistake per billion nucleotides incorporated. With an estimated 40,000 genes and three billion base pairs, the human genome needs to be replicated every time before a cell divides: DNA replication must work very fast, but more importantly, with great precision. Proofreading and error-checking mechanisms ensure the accuracy of the whole process. In eukaryote, several hours are needed to complete the DNA replication process despite the synthesis rate of 30,000 nucleotides per minute. Due to the complexity of eukaryotic genome, DNA replication on a strand is started simultaneously at several origins.
Hereditary Colorectal Cancer
Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams in Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Accurate DNA replication is essential to the integrity of any cellular organism. DNA is the ‘molecule of life’ as it carries the codes for every protein used to sustain and subserve cellular function. The fidelity of DNA replication is protected by multiple, overlapping systems of DNA repair. The most common of these are shown in Table 42.2. When one of these systems fails, errors in DNA replication can be transmitted to all the daughter cells and each generation of their offspring, and are incorporated into their genomes as mutations. Because of the redundancy in the genetic code, many mutations (especially point mutations) have no deleterious effects, but the mutator phenotype created by failure of DNA repair produces so many mutations that some are inevitably harmful. Some affect driver genes and can begin, and then sustain, carcinogenesis. Table 42.2 shows the syndromes of hereditary cancer associated with loss of the various systems of DNA repair.
Hormonal Regulation of Cell Proliferation and Differentiation
Jean Morisset, Travis E. Solomon in Growth of the Gastrointestinal Tract: Gastrointestinal Hormones and Growth Factors, 2017
In order for a eukaryotic cell to divide, it has to replicate its genome during the S phase of the cell cycle.1 Several lines of evidence indicate that DNA polymerase alpha is one of the principal enzymes that is involved in the regulation of DNA replication. Thus, aphidicolin, a specific inhibitor of this enzyme, inhibits DNA replication.37 Monoclonal antibodies against the enzyme also inhibit DNA synthesis.38,39 Enhanced activity of the enzyme correlates with enhanced DNA synthesis.40 A cell line that exhibits a temperature-sensitive defect in DNA replication is also a DNA polymerase alpha mutant.41 Although there is a slight increase in the expression of this enzyme prior to the S phase, and a slight decrease through the G2 phase, the enzyme is generally constitutively expressed throughout the cell cycle.42 Nonetheless, the regulation of the expression of this enzyme is believed to occur at the transcriptional level.42 Taken together, these observations indicate that enzymes which are involved in the regulation of cell proliferation are not necessarily active only during a specific phase of the cell cycle and that a variety of intracellular factors probably interact with cell cycle specific enzymes to regulate the exact timing of the proliferative response.
Overexpression of long non-coding RNA MCM3AP-AS1 in breast cancer tissues compared to adjacent non-tumour tissues
Published in British Journal of Biomedical Science, 2021
A Riahi, M Hosseinpour-Feizi, A Rajabi, M Akbarzadeh, V Montazeri, R Safaralizadeh
One of the essential elements of pre-replication complexes is minichromosome maintenance (MCM) proteins that are composed of six-component complexes (MCM2-MCM7) by DNA helicase activities. These complexes are involved in the initiation and extension processes of DNA replication and lead to restrictions of DNA replication to once per cell cycle. Minichromosome maintenance complex component 3-associated protein (MCM3AP) is located at 21q22.3, and codes for a protein that binds to and acetylates MCM3 through acetyltransferase functions. The interaction of MCM3AP with MCM3 is crucial for not only its entry into the nucleus but also its binding to chromatin. Increased MCM3AP expression level plays a role in inhibiting the S phase of the cell cycle, and its regulatory role as a tumour suppressor gene with a low level of expression has been proved in breast cancer. MCM3AP-AS1 is a long non-coding RNA antisense1 for MCM3AP [16–19]. The roles and regulatory mechanisms of lncRNA MCM3AP-AS1 in breast cancer are unclear.
Proteome of thymus and spleen reveals that 10-hydroxydec-2-enoic acid could enhance immunity in mice
Published in Expert Opinion on Therapeutic Targets, 2020
Pei Fan, Bin Han, Han Hu, Qiaohong Wei, Xufeng Zhang, Lifeng Meng, Jing Nie, Xiaofeng Tang, Xinyue Tian, Lu Zhang, Liping Wang, Jianke Li
DNA/RNA/protein activities are essential for cell growth and T cell functions for immune responses. CP has an impact on DNA activities, which is induced by acrolein, the metabolite of CP; thus, this causes DNA damage and DNA strands to break [32]. DNA replication is vital for cell proliferation and differentiation [33]. Given that thymocytes during the differentiation process are composed mostly of the thymus mass, the reduced thymic weight and thymic index of CP-induced mice may result from the decrease of thymocytes, which is associated with DNA replication. However, in 10-HDA treated thymus with CP induction, the retrieved function of DNA replication is suggestive of the fact that 10-HDA may increase the thymocyte number in the thymus via the reinforcement of DNA replication. Moreover, several other GO terms relevant to DNA/chromosome activities engaging in cell division/growth are also inhibited by CP, but revived by 10-HDA administration. For instance, DNA topological change, a crucial process for DNA replication, is always accompanied by ATP-dependent chromatin remodeling [34]. Hence, these findings are indicative of the fact that 10-HDA plays key roles in reviving DNA activities, thereby recovering thymic weight and increasing thymic index in mice.
Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Supreet Kaur, Nicholas S. Nieto, Peter McDonald, Josh R. Beck, Richard B. Honzatko, Anuradha Roy, Scott W. Nelson
Nearly 600 proteins exist within the apicoplast and approximately 4% of those are involved in replication of the 35 kb apicoplast genome12. Enzymes that carry-out the fundamental process of DNA replication are promising drug targets. Indeed, ciprofloxacin, a DNA type II topoisomerase inhibitor, has anti-malarial activity; however, antiparasitic properties could be due to off-target effects instead of, or as well as, inhibition of the P. falciparum gyrase13 The apicoplast DNA polymerase (apPOL) represents an attractive target for anti-malarial drug development14. apPOL exhibits low amino-acid sequence identity to replicative polymerases from other species. Outside of Apicomplexa, the nearest homolog (35% sequence identity) is the replicative polymerase from the cyanobacteria Cyanothece sp. PCC 8802. The most similar human DNA polymerases are the lesion bypass polymerases theta and nu (23% and 22% sequence identity, respectively), with the other human DNA polymerases displaying less than 20% identity, providing a foundation for selectivity. On the other hand, apPOLs from the two primary causative agents of human Malaria (P. falciparum and P. vivax) are 84% sequence identical, suggesting that drugs targeting P. falciparum apPOL would be effective in treating Malaria caused by P. vivax.
Related Knowledge Centers
- Biological Process
- Complementary DNA
- DNA
- Heredity
- Molecular Biology
- Origin of Replication
- Semiconservative Replication
- Nucleic Acid Double Helix
- Proofreading
- Cell
- Origin of Replication