Cell division
Frank J. Dye in Human Life Before Birth, 2019
In a population of dividing (called cycling) cells, each cell passes through four consecutive stages: G1, S, G2, and M (gap 1, DNA synthesis, gap 2, and mitosis). During G1, preparations are made for DNA synthesis; this is the stage that usually occupies the longest portion of the cell cycle. Also, differences in the duration of cell cycles between different kinds of cells can usually be attributed to differences in the duration of G1. DNA undergoes a process called semiconservative replication during the S stage. The two complementary strands of the mother cell's DNA separate, and each one acts as a template (a guide; see details in Chapter 4) for a new complementary strand. Barring mutations, two complete identical copies of the original DNA are formed (Figure 3.2).
DNA Repair and Carcinogenesis
Philip L. Grover in Chemical Carcinogens and DNA, 2019
In these experiments DNA, newly synthesized during semiconservative replication, is labeled by a short pulse soon after exposure to the agent, and its initial size is determined. Then DNA synthesis is allowed to continue for several hours in the absence of label (chase), and the original pulse-labeled DNA is again examined for size using alkaline sucrose gradients or similar techniques. Pulse-labeled DNA is eventually found to reach the size of the DNA from untreated cells. Since there is good evidence in bacteria that daughter strands of DNA made from UV-irradiated templates contain gaps (Figure 1C), Lehmann suggested that in UV-irradiated mammalian cells similar gaps are left in daughter strands when the DNA polymerase encounters a blocking lesion.72 The fact that the smaller DNA eventually reaches the size of DNA from unirradiated control cells suggests that during the chase such gaps are filled in some way. He72 and others73,74,77 could find no evidence that the gaps were filled by physical exchange between parental strands and daughter strands, and suggested, rather, that de novo synthesis is involved. If radioactive, pulse-labeled, low-molecular-weight DNA is chased in the presence of BUdR and then the DNA is subjected to 313-nm photolysis, its size is reduced once again to the original low molecular weight. This supports the hypothesis that the original shorter segments were interrupted by gaps which got filled by de novo synthesis utilizing the BUdR.
Poly (ADP-Ribose) Polymerase — A Nonhistone Nuclear Protein
Lubomir S. Hnilica in Chromosomal Nonhistone Proteins, 2018
The implication of poly (ADP-ribose) polymerase in DNA replication arises from observations where its enzymatic activity was found to be higher in proliferating cells than in quiescent cells. Such observations have included studies with mitogen-stimulated lympho cytes, SV40 transformed cells, hormone stimulated oviducts, hepatomas, and regenerating rat liver cells.14,19 In several studies the increase in polymerase activity was paralleled by an increase in DNA content, however, in others the increase far exceeded the rate of DNA synthesis. In studies by Lehmann et al.15 the use of inhibitors of DNA synthesis suggests that during semiconservative replication the synthesis of poly (ADP-ribose) and DNA are two independent events occurring during S-phase.
Cutis marmorata telangiectatica congenita: a focus on its diagnosis, ophthalmic anomalies, and possible etiologic factors
Published in Ophthalmic Genetics, 2020
Matthew S. Elitt, Joan E. Tamburro, Rocio T. Moran, Elias Traboulsi
In 1986 Rudolf Happle postulated the complex mechanism of mosaicism with embryonically lethal genetic mutations, providing an explanation for the unusual cutaneous disease patterns and non-mendelian inheritance seen in several disorders, including CMTC (39). In this concept, an embryonically lethal dominant or recessive mutation would emerge in a cell at the post-zygotic stage through a spontaneous mutation or semiconservative replication of a half-chromatid mutation, creating a mosaic embryo containing both genetically normal and abnormal tissues. Critically, Happle claimed that this unique developmental timeline would protect the embryo from mutation-induced fetal demise while also presenting a heritability block due to the embryonic lethality when present at the zygotic stage. Collectively, this idea could explain two prominent features of CMTC: (1) The presence of normal tissue outside of the vascular lesions and (2) non-mendelian inheritance patterns (5). However, rare reports of generational inheritance (40) and CMTC in sibling family members (41) present problems for this etiologic explanation which is predicated on a lack of heritability. To address this apparent conflict, Danarti, Konig, and Happle suggested a paradominant mode inheritance for CMTC (31,42), representing a slight modification to Happle’s original mosaicism model. In this idea mutations would be embryonically lethal when homozygous but tolerated when heterozygous, allowing for generational inheritance in carriers but precluding the emergence of non-mosaic, homozygous individuals. Similar to Happle’s original proposal, if a loss of heterozygosity occurred at a post-zygotic stage due to recombination, gene conversion, or a spontaneous mutation (43), and generated a mosaic embryo containing both genetically normal and abnormal tissue, the mutant cells could be tolerated (31). As such this could explain the potential for rare inheritance in CMTC while still satisfying non-mendelian inheritance and cutaneous lesion patterns seen in the disease.
An update on the biology and management of dyskeratosis congenita and related telomere biology disorders
Published in Expert Review of Hematology, 2019
Marena R. Niewisch, Sharon A. Savage
Telomere structure poses two main challenges related to DNA repair and replication: 1) they may be recognized by DNA damage repair machinery as double-stranded DNA breaks, and 2) the ‘end replication problem’ that results in ongoing telomere nucleotide repeat loss due to semiconservative replication of DNA ends during DNA replication.
Related Knowledge Centers
- DNA Replication
- Helicase
- Methylation
- Mutation
- Origin of Replication
- Phenotype
- Topoisomerase
- Origin of Replication
- Meselson–Stahl Experiment
- Isotopes of Nitrogen
- Nucleic Acid Double Helix