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At least 1,009 records · Page 56Linked to original sources
PubMed1974

Dominance of the senescent phenotype in heterokaryons between replicative and post-replicative human fibroblast-like cells.

In heterokaryons between senescent and young diploid fibroblast-like cells, dominance of the former with respect to nuclear DNA synthesis (incorporation of [(3)H]thymidine) was demonstrated. For identification of the respective partners, double-layer autoradiography was used after the old cells were labeled with [(3)H]methionine and the young cells were labeled with [(14)C]thymidine. Synchrony of nuclear labeling (i.e., all nuclei in a cell labeled with [(3)H]thymidine) was observed in the majority of di- and polykaryons during the second and third of three 24-hr periods of labeling with [(3)H]thymidine. The results are compatible with either terminal differentiation or error theories of clonal senescence.

Adolescent↗
PubMed1981

Kinetics of cell replication of the uterine cervix. V. Behavior of DNA-replicating tumor cells in invasive squamous carcinomas in mice.

The intratumoral migration of tritiated thymidine ([3H]dThd)-labeled cells was recorded at various intervals (from 1 to 240 hr) in squamous invasive carcinomas of the cervix in 25 inbred C57Bl mice. Carcinomas were induced by local application of benzo[a]pyrene for 5 months. This treatment was discontinued 7 days before the animals were killed. Cells were labeled by a single ip injection of 6 muCi [3H]dThd/g body weight. The tumors were divided by the aid of an ocular scale into three equal compartments: a peripheral zone, an intermediate zone, and a central zone. Many densely (initially) labeled cells were present in the peripheral and intermediate zones 1-48 hours after the injection of isotope, but these cells decreased in number in the intermediate zone and had disappeared from the peripheral zone by 96 hours. Conversely, densely labeled cells were absent in the center of the tumor during the first 24 hours, but they were recorded in large numbers at 48 hours. It was concluded that in addition to already known mechanisms of cell migration in solid tumors (e.g., invasion of the surrounding normal tissue, intravascular migration, migration toward the center of individual tumor nests, and cell exfoliation), there is intratumoral migration of cells toward the center in cervical carcinomas in mice.

Animals↗
PubMed2001

Early gene expression of vaccinia virus strains replicating (Praha) and non-replicating (modified vaccinia virus strain Ankara, MVA) in mammalian cells.

Modified vaccinia virus Ankara strain (MVA) is a safe highly attenuated non-pathogenic virus suitable as a vector for developing various vaccines. Study of expression of a reporter beta-galactosidase gene under the control of an early vaccinia virus (VV) promoter in MVA and non-modified vaccinia virus Praha strain showed that early transcription in MVA is elevated in comparison with non modified VV. This property was demonstrated in various cell cultures including CV1 cells, human lung diploid cells, chicken primary fibroblasts but not in bone marrow-derived mouse dendritic cells. There the relationship between the elevated early transcription and the permisivity of cells for MVA was not observed.

Animals↗
PubMed2006

Temporal order of evolution of DNA replication systems inferred by comparison of cellular and viral DNA polymerases.

BACKGROUND: The core enzymes of the DNA replication systems show striking diversity among cellular life forms and more so among viruses. In particular, and counter-intuitively, given the central role of DNA in all cells and the mechanistic uniformity of replication, the core enzymes of the replication systems of bacteria and archaea (as well as eukaryotes) are unrelated or extremely distantly related. Viruses and plasmids, in addition, possess at least two unique DNA replication systems, namely, the protein-primed and rolling circle modalities of replication. This unexpected diversity makes the origin and evolution of DNA replication systems a particularly challenging and intriguing problem in evolutionary biology. RESULTS: I propose a specific succession for the emergence of different DNA replication systems, drawing argument from the differences in their representation among viruses and other selfish replicating elements. In a striking pattern, the DNA replication systems of viruses infecting bacteria and eukaryotes are dominated by the archaeal-type B-family DNA polymerase (PolB) whereas the bacterial replicative DNA polymerase (PolC) is present only in a handful of bacteriophage genomes. There is no apparent mechanistic impediment to the involvement of the bacterial-type replication machinery in viral DNA replication. Therefore, I hypothesize that the observed, markedly unequal distribution of the replicative DNA polymerases among the known cellular and viral replication systems has a historical explanation. I propose that, among the two types of DNA replication machineries that are found in extant life forms, the archaeal-type, PolB-based system evolved first and had already given rise to a variety of diverse viruses and other selfish elements before the advent of the bacterial, PolC-based machinery. Conceivably, at that stage of evolution, the niches for DNA-viral reproduction have been already filled with viruses replicating with the help of the archaeal system, and viruses with the bacterial system never took off. I further suggest that the two other systems of DNA replication, the rolling circle mechanism and the protein-primed mechanism, which are represented in diverse selfish elements, also evolved prior to the emergence of the bacterial replication system. This hypothesis is compatible with the distinct structural affinities of PolB, which has the palm-domain fold shared with reverse transcriptases and RNA-dependent RNA polymerases, and PolC that has a distinct, unrelated nucleotidyltransferase fold. I propose that PolB is a descendant of polymerases that were involved in the replication of genetic elements in the RNA-protein world, prior to the emergence of DNA replication. By contrast, PolC might have evolved from an ancient non-templated polymerase, e.g., polyA polymerase. The proposed temporal succession of the evolving DNA replication systems does not depend on the specific scenario adopted for the evolution of cells and viruses, i.e., whether viruses are derived from cells or virus-like elements are thought to originate from a primordial gene pool. However, arguments are presented in favor of the latter scenario as the most parsimonious explanation of the evolution of DNA replication systems. CONCLUSION: Comparative analysis of the diversity of genomic strategies and organizations of viruses and cellular life forms has the potential to open windows into the deep past of life's evolution, especially, with the regard to the origin of genome replication systems. When complemented with information on the evolution of the relevant protein folds, this comparative approach can yield credible scenarios for very early steps of evolution that otherwise appear to be out of reach. REVIEWERS: Eric Bapteste, Patrick Forterre, and Mark Ragan.

Journal Article↗
PubMed1998

Cellular proteins required for adeno-associated virus DNA replication in the absence of adenovirus coinfection.

We previously reported the development of an in vitro adeno-associated virus (AAV) DNA replication system. The system required one of the p5 Rep proteins encoded by AAV (either Rep78 or Rep68) and a crude adenovirus (Ad)-infected HeLa cell cytoplasmic extract to catalyze origin of replication-dependent AAV DNA replication. However, in addition to fully permissive DNA replication, which occurs in the presence of Ad, AAV is also capable of partially permissive DNA replication in the absence of the helper virus in cells that have been treated with genotoxic agents. Limited DNA replication also occurs in the absence of Ad during the process of establishing a latent infection. In an attempt to isolate uninfected extracts that would support AAV DNA replication, we discovered that HeLa cell extracts grown to high density can occasionally display as much in vitro replication activity as Ad-infected extracts. This finding confirmed previous genetic analyses which suggested that no Ad-encoded proteins were absolutely essential for AAV DNA replication and that the uninfected extracts should be useful for studying the differences between helper-dependent and helper-independent AAV DNA replication. Using specific chemical inhibitors and monoclonal antibodies, as well as the fractionation of uninfected HeLa extracts, we identified several of the cellular enzymes involved in AAV DNA replication. They were the single-stranded DNA binding protein, replication protein A (RFA), the 3' primer binding complex, replication factor C (RFC), and proliferating cell nuclear antigen (PCNA). Consistent with the current model for AAV DNA replication, which requires only leading-strand DNA synthesis, we found no requirement for DNA polymerase alpha-primase. AAV DNA replication could be reconstituted with purified Rep78, RPA, RFC, and PCNA and a phosphocellulose chromatography fraction (IIA) that contained DNA polymerase activity. As both RFC and PCNA are known to be accessory proteins for polymerase delta and epsilon, we attempted to reconstitute AAV DNA replication by substituting either purified polymerase delta or polymerase epsilon for fraction IIA. These attempts were unsuccessful and suggested that some novel cellular protein or modification was required for AAV DNA replication that had not been previously identified. Finally, we also further characterized the in vitro DNA replication assay and demonstrated by two-dimensional (2D) gel electrophoresis that all of the intermediates commonly seen in vivo are generated in the in vitro system. The only difference was an accumulation of single-stranded DNA in vivo that was not seen in vitro. The 2D data also suggested that although both Rep78 and Rep68 can generate dimeric intermediates in vitro, Rep68 is more efficient in processing dimers to monomer duplex DNA. Regardless of the Rep that was used in vitro, we found evidence of an interaction between the elongation complex and the terminal repeats. Nicking at the terminal repeats of a replicating molecule appeared to be inhibited until after elongation was complete.

Adenoviridae↗
PubMed1993

Recovery of DNA replication in UV-damaged Escherichia coli.

Following exposure to UV light DNA replication stops and then resumes. The SOS response is required for the restoration of replication. Replication recovery occurs in lexA(Ind) cells carrying a high constitutive level of RecA protein. Replication is also affected by UmuCD proteins, photoreactivation, and excision repair. In addition, there is a constitutive and recA independent way to replicate over UV photoproducts associated with the production of gaps in daughter DNA strands. There are two ways to account for the replication in UV-irradiated cells. A stalled replication fork can be reactivated. Alternatively, a replication fork could be destroyed irreparably, with no available way to complete the round of replication. In that case, postirradiation replication could be due exclusively to replication forks assembled de novo at the origin(s). Changes in replication initiation are observed following UV irradiation. Initiations are first inhibited and then stimulated. They become independent of de novo protein synthesis and sometimes do not stop in dnaA(ts) mutants shifted to 42 degrees C. Although the inducible functions are involved in the recovery of replication at different levels of UV damage, some modifications of the replication initiation mechanism appear to be specific to severely damaged cells. Such modifications seem to include the dnaA(ts) independence for initiations and the transient initiation inhibition. RecA protein can be directly involved both in the modification of initiation and in reactivation of the stalled replication forks. Although the restoration of replication depends on the SOS response a synthesis of some protein(s) that do not belong to the LexA regulon seems to be required as well. These proteins can be under RecA control and one of their functions may be to inhibit the rnhA gene. Certain recA mutations may selectively affect different mechanisms of the replication recovery (namely, recA430, recA727, recA718, recA1730). Overproduction of the photoreactivating enzyme in the dark could influence UmuCD activity in replication. The UmuCD function appears to be blocked in strains carrying the dnaE1026 mutation or overproducing the dnaQ protein. For some unknown reason the UmuCD-associated replication mechanism is the only one available for phage with damaged DNA.

DNA Damage↗