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Effects of Folic Acid Deficiency on Tumor Cell Biology
Published in Maryce M. Jacobs, Vitamins and Minerals in the Prevention and Treatment of Cancer, 2018
Direct evidence that DNA synthesis is impaired in folate deficient cells was provided by measurements showing that the migration of the DNA replication fork and the joining of Okazaki fragments are delayed. DNA molecules do not replicate continuously from one end to the other. They are subdivided into segments which have an origin and a terminus. The replicating fork is the point at which the two parental strands separate.42 Within the replicating segments, synthesis occurs in short pieces approximately 50 to 150 nucleotides long called Okazaki fragments. These segments are joined together by removal of the RNA primer and gap-filling by further DNA synthesis.42
Introduction to Telomere Biology
Published in Sara C. Zapico, Mechanisms Linking Aging, Diseases and Biological Age Estimation, 2017
Celia de Frutos, Pablo Bermejo-Álvarez
During cellular replication, the lineal chromosome of eukaryotes suffers from a telomere shortening on each mitosis estimated at 100 bp in humans, due to the DNA replication process. DNA replication in eukaryotes is a semiconservative process, which means that it is carried out by copying the parental DNA strand, as originally suggested by Watson and Crick model (Watson and Crick 1953a). DNA replication starts by separating both strands of the double helix of DNA, which leaves one strand oriented in 5’-3’ sense and the other in reverse sense. The enzyme responsible for the de novo synthesis of DNA, the DNA polymerase, can only synthesize in the 5’-3’ sense, requiring a small oligonucleotide sequence (RNA primer) to start replication. The strand synthesized in that sense, called leading strand, is continuously synthesized to the end of the template strand. The end replication problem arises in the complementary strand, oriented in 3’-5’ sense. On this strand, the nascent DNA strand, called lagging strand, requires to be synthesized by small and discontinuous fragments, named Okazaki fragments, which are later bound by a ligase, replacing the RNA primers by DNA. As ligase requires a DNA strand in front of the primer, the last RNA primer is removed and therefore, DNA polymerase is unable to replicate the 3’ end from the template strand and the sequence is shortened in each mitotic cycle (Fig. 1).
Biology of microbes
Published in Philip A. Geis, Cosmetic Microbiology, 2006
This process leaves a series of completed double helix fragments of DNA called Okazaki fragments (named after their discoverer), separated by incomplete gaps along the DNA strand. These gaps are filled in by the DNA ligase enzyme. Meanwhile, leading strands are made continuously. A variety of single stranded DNA binding proteins keeps the single strands apart until the polymerase and ligase can complete the addition of complementary nucleotides. The topoisomerases relieve the tension on the double helix in advance of the gyrase. Repair nucleases recognize errors in replication and remove incorrect nucleotides to allow the polymerases and ligases to replace them with the correct nucleotides.
Emergence of varicella-zoster virus resistance to acyclovir: epidemiology, prevention, and treatment
Published in Expert Review of Anti-infective Therapy, 2021
Kimiyasu Shiraki, Masaya Takemoto, Tohru Daikoku
Double-stranded DNA needs to be separated into two single strands (replication fork) before DNA synthesis, and complementary strands are synthesized from each DNA strand to produce two new double-stranded DNA molecules during DNA replication (Figure 3). The HP complex is responsible for unwinding viral DNA at the replication fork, separating double-stranded DNA into two single strands, and synthesizing RNA primers (Okazaki fragments) in the lagging strand for DNA synthesis. DNApol initiates complementary DNA synthesis in the two separated DNA strands. The HP complex consists of three proteins: VZVORF55 (helicase), VZVORF6 (primase), and VZVORF52 (cofactor). The helicase unwinds the duplex DNA ahead of the fork and separates the double strand into two single strands. The primase lays down RNA primers that extend the two-subunit DNApol. The HP complex possesses multienzymatic activities, including DNA-dependent ATPase, helicase, and primase activities, all of which are required for the HP complex to function in viral DNA replication.
Telomere length measurement as a clinical biomarker of aging and disease
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Telomere length, DNA replication, and replicative capacity. Recently, Gadalla et al. [39] showed improved survival among recipients of bone marrow transplants for treatment of aplastic anemia when donor tissues had longer telomere lengths [39]. This increase in survival was attributed to an increase in telomere-mediated replicative capacity that helped reestablish a productive hematopoietic system. Because post-replicative removal of the Okazaki fragment generates a gap and a single-stranded 3′ DNA overhang, telomeres shorten after every cell division in a process known as “the end-replication problem” [1] (Figure 1(C)). Eventually, telomeres reach a point of critical shortness, after which cells enter a senescent state of permanent growth arrest [1]. Telomere attrition has long been associated with cellular aging and provides proliferating cells with a means to determine cellular lifespan [2] or replicative capacity. Genetic predisposition for longer telomere lengths has been associated with increased cancer risk [34,40,41]. Simply, longer telomere lengths promote more cell divisions prior to senescence or cell death [1]. As bone marrow transplant recipients exemplify [39], repopulating a cellular niche necessitates sufficient telomere-mediated replicative capacity for success.
Curcumin restrains hepatocellular carcinoma progression depending on the regulation of the circ_0078710/miR-378b/PRIM2 axis
Published in Journal of Receptors and Signal Transduction, 2022
Qian Chen, Hai Guo, Yan Zong, Xiaofeng Zhao
MiRNAs have shown important regulatory roles in gene expression by interacting with the 3′ untranslated region (3′UTR) of messenger RNAs (mRNAs) [16]. Through using TargetScan database, DNA primase, polypeptide 2 (PRIM2) was predicted as a possible target of miR-378b. PRIM2 is a subunit of DNA primer enzyme. DNA primer enzyme regulates the initiation of DNA replication and the synthesis of Okazaki fragments [17,18]. Liu et al. found that SIX1 promoted the DNA synthesis, cell cycle progression, and proliferation of cervical cancer cells by up-regulating PRIM2 level [19]. In this study, the interaction between PRIM2 and miR-378b along with their functional association in HCC were explored.