RESUMO
Based on the morphology of gametes, sexual reproduction in brown algae is usually classified into three types: isogamy, anisogamy, and oogamy. In isogamy, chloroplasts and chloroplast DNA (chlDNA) in the sporophyte cells are inherited biparentally, while mitochondria (or mitochondrial DNA, mtDNA) is inherited maternally. In oogamy, chloroplasts and mitochondria are inherited maternally. However, the patterns of mitochondrial and chloroplast inheritance in anisogamy have not been clarified. Here, we examined derivation of mtDNA and chlDNA in the zygotes through strain-specific PCR analysis using primers based on single nucleotide polymorphism in the anisogamous brown alga Mutimo cylindricus. In 20-day-old sporophytes after fertilization, mtDNA and chlDNA derived from female gametes were detected, thus confirming the maternal inheritance of both organelles. Additionally, the behavior of mitochondria and chloroplasts in the zygotes was analyzed by examining the consecutive serial sections using transmission electron microscopy. Male mitochondria were isolated or compartmentalized by a double-membrane and then completely digested into a multivesicular structure 2 h after fertilization. Meanwhile, male chloroplasts with eyespots were observed even in 4-day-old, seven-celled sporophytes. The final fate of male chloroplasts could not be traced. Organelle DNA copy number was also examined in female and male gametes. The DNA copy number per chloroplast and mitochondria in male gametes was lower compared with female organelles. The degree of difference is bigger in mtDNA. Thus, changes in different morphology and DNA amount indicate that maternal inheritance of mitochondria and chloroplasts in this species may be based on different processes and timing after fertilization.
Assuntos
Cloroplastos/metabolismo , Herança Extracromossômica/fisiologia , Mitocôndrias/metabolismo , Phaeophyceae/metabolismo , Feminino , Humanos , MasculinoRESUMO
Macroautophagic degradation of sperm-inherited organelles prevents paternal mitochondrial DNA transmission in C. elegans. The recruitment of autophagy markers around sperm mitochondria has also been observed in mouse and fly embryos but their role in degradation is debated. Both worm Atg8 ubiquitin-like proteins, LGG-1/GABARAP and LGG-2/LC3, are recruited around sperm organelles after fertilization. Whereas LGG-1 depletion affects autophagosome function, stabilizes the substrates and is lethal, we demonstrate that LGG-2 is dispensable for autophagosome formation but participates in their microtubule-dependent transport toward the pericentrosomal area prior to acidification. In the absence of LGG-2, autophagosomes and their substrates remain clustered at the cell cortex, away from the centrosomes and their associated lysosomes. Thus, the clearance of sperm organelles is delayed and their segregation between blastomeres prevented. This allowed us to reveal a role of the RAB-5/RAB-7 GTPases in autophagosome formation. In conclusion, the major contribution of LGG-2 in sperm-inherited organelle clearance resides in its capacity to mediate the retrograde transport of autophagosomes rather than their fusion with acidic compartments: a potential key function of LC3 in controlling the fate of sperm mitochondria in other species.
Assuntos
Autofagia/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Organelas/metabolismo , Espermatozoides/citologia , Animais , Transporte Biológico , Herança Extracromossômica/fisiologia , Imunofluorescência , Masculino , Microscopia Eletrônica de Transmissão , Interferência de RNARESUMO
Transgenerational inheritance of environment induced phenotype requires transmission of epigenetic information through the germline. Whereas several epigenetic factors have been implicated in germline transmission, mediators of information transfer from soma to the germline remain unidentified in mammals. Notably, a recent bioinformatic analysis showed association of extracellular microRNAs (miRNAs) and altered transcriptomes in diverse instances of mammalian epigenetic inheritance involving different environmental factors, tissues, life cycle stages, generations and genders. It was predicted that regulatory non-coding RNAs (ncRNAs) may potentially mediate soma to germline information transfer. Remarkably, the present bioinformatic evidence suggests similar association of exosomal mRNAs and proteins. The differentially expressed genes reported previously in genome level expression profiling studies related to or relevant in epigenetic inheritance showed enrichment for documented set of exosomal mRNAs in a few instances of epigenetic inheritance and of exosomal proteins in a majority of instances. Differentially expressed genes encoding exosomal miRNAs and proteins, directly or indirectly through first and/or second degree interactome networks, overrepresented biological processes related to environmental factors used in these instances as well as to epigenetic alterations, especially chromatin and histone modifications. These findings predict that exosomal mRNAs and proteins, like extracellular miRNAs, may also potentially mediate soma to germline information transfer. A convergent conceptual model is presented wherein extracellular ncRNAs/miRNA, mRNAs and proteins provide the much needed continuum inclusive of epigenetic inheritance. The phrase "transgenerational systems biology" is introduced to signify that the realm of systems biology extends beyond an individual organism and encompasses generations.
Assuntos
Epigênese Genética/fisiologia , Exossomos , Herança Extracromossômica/fisiologia , Modelos Genéticos , Proteínas , Animais , Biologia Computacional , Exossomos/genética , Exossomos/metabolismo , Proteínas/genética , Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RatosRESUMO
The past decade has seen an explosion of articles in scientific journals involving non-genetic influences on phenotype through modulation of gene function without changes in gene sequence. The excitement in modern molecular biology surrounding the impact exerted by the environment on development of the phenotype is focused largely on mechanism and has not incorporated questions asked (and answers provided) by early philosophers, biologists, and psychologists. As such, this emergence of epigenetic studies is somewhat "old wine in new bottles" and represents a reformulation of the old debate of preformationism versus epigenesis-one resolved in the 1800s. Indeed, this tendency to always look forward, with minimal concern or regard of what has gone before, has led to the present situation in which "true" epigenetic studies are believed to consist of one of two schools. The first is primarily medically based and views epigenetic mechanisms as pathways for disease (e.g., "the epigenetics of cancer"). The second is primarily from the basic sciences, particularly molecular genetics, and regards epigenetics as a potentially important mechanism for organisms exposed to variable environments across multiple generations. There is, however, a third, and separate, school based on the historical literature and debates and regards epigenetics as more of a perspective than a phenomenon. Against this backdrop, comparative integrative biologists are particularly well-suited to understand epigenetic phenomena as a way for organisms to respond rapidly with modified phenotypes (relative to natural selection) to changes in the environment. Using evolutionary principles, it is also possible to interpret "sunsetting" of modified phenotypes when environmental conditions result in a disappearance of the epigenetic modification of gene regulation. Comparative integrative biologists also recognize epigenetics as a potentially confounding source of variation in their data. Epigenetic modification of phenotype (molecular, cellular, morphological, physiological, and behavioral) can be highly variable depending upon ancestral environmental exposure and can contribute to apparent "random" noise in collected datasets. Thus, future research should go beyond the study of epigenetic mechanisms at the level of the gene and devote additional investigation of epigenetic outcomes at the level of both the individual organism and how it affects the evolution of populations. This review is the first of seven in this special issue of Integrative and Comparative Biology that addresses in detail these and other key topics in the study of epigenetics.
Assuntos
Adaptação Biológica/genética , Evolução Biológica , Meio Ambiente , Epigênese Genética/fisiologia , Epigenômica/métodos , Fenótipo , Pesquisa , Herança Extracromossômica/fisiologia , Padrões de Herança/fisiologiaRESUMO
In addition to their nuclear genome, the vast majority of eukaryotes harbour cytoplasmic genomes, e.g. in mitochondria or chloroplasts. In the majority of cases, these cytoplasmic genomes are transmitted maternally only, leading to selective pressures divergent from those that act on nuclear genes. In particular, cytoplasmic genes, which reduce the fitness of males that carry them, but have no fitness effect in females, are believed to be selectively neutral. Here, we go a step further and argue that in outbreeding populations (i.e. populations with inbreeding avoidance), 'spiteful' cytoplasmic elements that reduce the number of offspring produced by males are in fact selected for. We study this process by means of a stochastic model, analysing both the probability of spread and the impact that such a spiteful cytotype can have on population dynamics. Our results demonstrate that the probability of spread of the spiteful cytotype can be several times higher in outbreeding than in panmictic populations. Spread and fixation of the spiteful cytotype can lead to different qualitative effects on the population dynamics, including extinction, decreased or increased stable population size. We discuss our results in respect to cytoplasmically induced male infertility and cytoplasmic incompatibility.
Assuntos
Cruzamento , Herança Extracromossômica/fisiologia , Comportamento Sexual Animal , Animais , Feminino , Infertilidade Masculina/genética , Masculino , Dinâmica Populacional , Wolbachia/genéticaRESUMO
Paul Kammerer's career ended in scandal in 1926 over tampering with his evidence for "Lamarckian" evolution--the infamous midwife toad. But although Kammerer's conclusions proved false, his evidence was probably genuine. In any case his arguments were not simply for Lamarckism and against Darwinism, as the theories are understood today. If we look beyond the scandal, the Kammerer story shows us a great deal about early 20th-century biology: the range of new ideas about heredity and variation, competing theories of biological and cultural evolution and their applications in eugenics, new kinds of laboratories and professional roles for biologists, and changing standards for documenting experimental results.
Assuntos
Biologia/história , Pessoas Famosas , Genética/história , Adaptação Fisiológica , Animais , Anuros/fisiologia , Áustria , Herança Extracromossômica/fisiologia , Feminino , História do Século XIX , História do Século XX , Humanos , Modelos Biológicos , Projetos de PesquisaRESUMO
Cells have evolved molecular mechanisms for the efficient transmission of organelles during cell division. Little is known about how peroxisomes are inherited. Inp1p is a peripheral membrane protein of peroxisomes of Saccharomyces cerevisiae that affects both the morphology of peroxisomes and their partitioning during cell division. In vivo 4-dimensional video microscopy showed an inability of mother cells to retain a subset of peroxisomes in dividing cells lacking the INP1 gene, whereas cells overexpressing INP1 exhibited immobilized peroxisomes that failed to be partitioned to the bud. Overproduced Inp1p localized to both peroxisomes and the cell cortex, supporting an interaction of Inp1p with specific structures lining the cell periphery. The levels of Inp1p vary with the cell cycle. Inp1p binds Pex25p, Pex30p, and Vps1p, which have been implicated in controlling peroxisome division. Our findings are consistent with Inp1p acting as a factor that retains peroxisomes in cells and controls peroxisome division. Inp1p is the first peroxisomal protein directly implicated in peroxisome inheritance.
Assuntos
Divisão Celular/fisiologia , Herança Extracromossômica/fisiologia , Membranas Intracelulares/metabolismo , Proteínas de Membrana/metabolismo , Peroxissomos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Ciclo Celular/fisiologia , Proteínas de Ligação ao GTP/metabolismo , Regulação Fúngica da Expressão Gênica/genética , Membranas Intracelulares/ultraestrutura , Proteínas de Membrana/genética , Peroxinas , Peroxissomos/genética , Peroxissomos/ultraestrutura , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Transporte VesicularRESUMO
Analyses of birth and weaning weights, fleece weights of ewes, and number born per litter of Polypay sheep collected at the U.S. Sheep Experimental Station from 1978 through 1998, confirmed previous analyses of three other dual-purpose breeds that cytoplasmic effects do not contribute to variation in these four traits. In general, estimates of genetic parameters that would be needed for national genetic evaluation were similar to previous estimates for Columbia, Rambouillet, and Targhee sheep, although estimates of direct heritability for Polypay were somewhat less for birth weight, slightly greater for weaning weight, significantly greater for fleece weight, and the same for number born as for those three breeds. For birth weight only, evidence was found for important dam x year or dam x number born interactions, which are essentially litter effects, as was found for the other dual-purpose breeds. There were 11,896, 11,104, 7,748, and 7,831 records for birth and weaning weights, fleece weight, and number born per litter, with 255 to 316 sires of animals with records. There were 260 and 261 cytoplasmic lines for fleece weight and number born, and 861 and 882 for weaning and birth weights.
Assuntos
Peso Corporal/genética , Herança Extracromossômica/genética , Tamanho da Ninhada de Vivíparos/genética , Modelos Genéticos , Ovinos/genética , Animais , Peso ao Nascer/genética , Peso ao Nascer/fisiologia , Peso Corporal/fisiologia , Cruzamento/métodos , Cruzamentos Genéticos , Herança Extracromossômica/fisiologia , Feminino , Funções Verossimilhança , Tamanho da Ninhada de Vivíparos/fisiologia , Masculino , Característica Quantitativa Herdável , Ovinos/fisiologia , Desmame , Lã/fisiologiaRESUMO
I investigated whether soil moisture affects relative fitness of females and hermaphrodites and sex ratio in a gynodioecious plant with nuclear-cytoplasmic sex inheritance. I contrast these results with those from species with strictly nuclear sex inheritance. I performed a manipulative watering experiment on seed fitness of the two sexes, and field studies measuring seed fitness and sex ratio as a function of soil moisture. In the dry site, watered hermaphrodites produced approximately twice as many seeds as unwatered hermaphrodites, with little treatment effect on female seed production. Over a natural soil moisture gradient, the ratio of female to hermaphrodite seed production was higher in dry than in wet sites. These data show that the seed fitness advantage of females is a function of soil moisture. Despite this, regression of soil moisture on the sex ratio of 23 populations was not significant. These results indicate a sex-dependent effect of soil moisture on resource allocation to seeds that does not translate into a strong effect on sex ratio. This is consistent with theory based on genomic conflict in which sex ratios are predicted to be only partly determined by fitness differences of the sexes.
Assuntos
Herança Extracromossômica/fisiologia , Hydrophyllaceae/fisiologia , Sementes/fisiologia , Razão de Masculinidade , Solo/análise , California , Análise de Regressão , Reprodução/fisiologia , Água/análiseAssuntos
Cryptococcus neoformans/fisiologia , Herança Extracromossômica/fisiologia , Proteínas Fúngicas/genética , Genes Homeobox/genética , Cruzamentos Genéticos , Cryptococcus neoformans/genética , DNA Mitocondrial/genética , Herança Extracromossômica/genética , Proteínas Fúngicas/fisiologia , Mapeamento por Restrição , Fatores de Transcrição/genéticaRESUMO
Calorie restriction is the only life span extending regimen known that applies to all aging organisms. Although most fungi do not appear to senesce, all natural isolates of the modular filamentous fungus Podospora anserina have a limited life span. In this paper, we show that calorie restriction extends life span also in Podospora anserina. The response to glucose limitation varies significantly among 23 natural isolates from a local population in The Netherlands, ranging from no effect up to a 5-fold life span extension. The isolate dependent effect is largely due to the presence or absence of pAL2-1 homologous plasmids. These mitochondrial plasmids are associated with reduced life span under calorie restricted conditions, suggesting a causal link. This has been substantiated using three combinations of isogenic isolates with and without plasmids. A model is proposed to explain how pAL2-1 homologues influence the response to calorie restriction.
Assuntos
Restrição Calórica , Mitocôndrias/genética , Plasmídeos , Sordariales/genética , Sordariales/fisiologia , DNA Fúngico/genética , DNA Fúngico/fisiologia , DNA Mitocondrial/genética , DNA Mitocondrial/fisiologia , Ingestão de Energia , Metabolismo Energético , Herança Extracromossômica/genética , Herança Extracromossômica/fisiologia , Partículas Submitocôndricas , Fatores de TempoRESUMO
The level of genomic DNA methylation plays an important role in development and disease. In order to establish an experimental system for the functional analysis of genome-wide hypermethylation, we overexpressed the mouse de novo methyltransferase Dnmt3a in Drosophila melanogaster. These flies showed severe developmental defects that could be linked to reduced rates of cell cycle progression and irregular chromosome condensation. In addition, hypermethylated chromosomes revealed elevated rates of histone H3-K9 methylation and a more restricted pattern of H3-S10 phosphorylation. The developmental and chromosomal defects induced by DNA hypermethylation could be rescued by mutant alleles of the histone H3-K9 methyltransferase gene Su(var)3-9. This mutation also resulted in a significantly decreased level of genomic DNA methylation. Our results thus uncover the molecular consequences of genomic hypermethylation and demonstrate a mutual interaction between DNA methylation and histone methylation.
Assuntos
Cromatina/metabolismo , Cromossomos/metabolismo , Metilação de DNA , Herança Extracromossômica/fisiologia , Histonas/metabolismo , Animais , Ciclo Celular/genética , Aberrações Cromossômicas , Cromossomos/genética , Drosophila melanogaster , Cariotipagem , Metiltransferases/genética , Mutagênese Sítio-Dirigida , Fenótipo , Fosforilação , Taxa de SobrevidaRESUMO
There is a risk that ICSI may increase the transmission of mtDNA diseases to children born after this technique. Knowledge of the fate and transmission of paternal mitochondrial DNA is important since mutations in mitochondrial DNA have been described in oligozoospermic males. We have used an adaptation of solid phase mini-sequencing to exclude the presence of levels of paternal mtDNA >0.001% in ICSI families. This method is more sensitive than those used in previous studies and is sufficient to detect the likely paternal contribution (approximately 0.1-0.5% from simple calculations of expected dilution during fertilization). Using this method, we were able to detect concentrations as low as 0.001% paternal mtDNA in a maternal mtDNA background. No paternal mtDNA was detected in the embryonic (blood or buccal swabs) tissue of children born after ICSI nor in extra-embryonic tissue (placenta or umbilical cord). In conclusion, we did not detect paternal mtDNA in blood, buccal swabs, placenta or umbilical cord of children born after ICSI. We have found no evidence that ICSI increases the risk of paternal transmission of mtDNA and hence of mtDNA disorders.
Assuntos
DNA Mitocondrial/análise , Herança Extracromossômica , Injeções de Esperma Intracitoplásmicas , DNA Mitocondrial/sangue , DNA Mitocondrial/genética , Herança Extracromossômica/fisiologia , Pai , Feminino , Humanos , Masculino , Mucosa Bucal/química , Mucosa Bucal/citologia , Mucosa Bucal/fisiologia , Oligospermia/terapia , Placenta/química , Placenta/fisiologia , Gravidez , Cordão Umbilical/química , Cordão Umbilical/fisiologiaRESUMO
Bacterial plasmids introduced into the human malaria parasite Plasmodium falciparum replicate well but are poorly segregated during mitosis. In this paper, we screened a random P.falciparum genomic library in order to identify sequences that overcome this segregation defect. Using this approach, we selected for parasites that harbor a unique 21 bp repeat sequence known as Rep20. Rep20 is one of six different repeats found in the subtelomeric regions of all P.falciparum chromosomes but which is not found in other eukaryotes or in other plasmodia. Using a number of approaches, we demonstrate that Rep20 sequences lead to dramatically improved episomal maintenance by promoting plasmid segregation between daughter merozoites. We show that Rep20(+), but not Rep20(-), plasmids co-localize with terminal chromosomal clusters, indicating that Rep20 mediates plasmid tethering to chromosomes, a mechanism that explains the improved segregation phenotype. This study implicates a direct role for Rep20 in the physical association of chromosome ends, which is a process that facilitates the generation of diversity in the terminally located P.falciparum virulence genes.
Assuntos
Segregação de Cromossomos/fisiologia , DNA de Protozoário/fisiologia , Herança Extracromossômica/fisiologia , Vetores Genéticos/genética , Plasmídeos/genética , Plasmodium falciparum/genética , Sequências Repetitivas de Ácido Nucleico , Animais , Segregação de Cromossomos/genética , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , DNA de Protozoário/genética , DNA Recombinante/genética , DNA Recombinante/metabolismo , Herança Extracromossômica/genética , Biblioteca Gênica , Mitose , Telômero/metabolismo , TransfecçãoRESUMO
The experimental evidence accumulated for the last half of the century clearly suggests that inherited variation is not restricted to the changes in genomic sequences. The prion model, originally based on unusual transmission of certain neurodegenerative diseases in mammals, provides a molecular mechanism for the template-like reproduction of alternative protein conformations. Recent data extend this model to protein-based genetic elements in yeast and other fungi. Reproduction and transmission of yeast protein-based genetic elements is controlled by the "prion replication" machinery of the cell, composed of the protein helpers responsible for the processes of assembly and disassembly of protein structures and multiprotein complexes. Among these, the stress-related chaperones of Hsp100 and Hsp70 groups play an important role. Alterations of levels or activity of these proteins result in "mutator" or "antimutator" affects in regard to protein-based genetic elements. "Protein mutagens" have also been identified that affect formation and/or propagation of the alternative protein conformations. Prion-forming abilities appear to be conserved in evolution, despite the divergence of the corresponding amino acid sequences. Moreover, a wide variety of proteins of different origins appear to possess the ability to form amyloid-like aggregates, that in certain conditions might potentially result in prion-like switches. This suggests a possible mechanism for the inheritance of acquired traits, postulated in the Lamarckian theory of evolution. The prion model also puts in doubt the notion that cloned animals are genetically identical to their genome donors, and suggests that genome sequence would not provide a complete information about the genetic makeup of an organism.
Assuntos
Herança Extracromossômica/fisiologia , Modelos Genéticos , Mutagênese/fisiologia , Proteínas/genética , Proteínas/metabolismo , Animais , Fungos/genética , Genes/fisiologia , Proteínas de Choque Térmico/fisiologia , Humanos , Substâncias Macromoleculares , Chaperonas Moleculares/fisiologia , Mutação/fisiologia , Príons/genética , Príons/metabolismo , Conformação ProteicaRESUMO
Using a semi-quantitative review of published electron micrographs, we have explored the passage of mitochondria from one generation to the next through the cytoplasm of the human female germ cell. We propose a testable hypothesis that the mitochondria of the germline are persistently 'haploid' (effectively carrying just one mitochondrial chromosome per organelle). For mitochondria, the passage through germ cell differentiation, oogenesis, follicle formation and loss could constitute a restriction/amplification/constraint event of a type previously demonstrated for asexual purification and refinement of a nonrecombining genome. At the restriction event (or 'bottleneck') in the human primordial germ cell, which differentiates in embryos after gastrulation, there appear to be <10 mitochondria per cell. From approximately 100 or so such cells, a population of > or =7 x 10(6) oogonia and primary oocytes is produced in the fetal ovaries during mid-gestation, with mitochondria numbering up to 10000 per cell, implying a massive amplification of the mitochondrial genome. A further 10-fold or greater increase in mitochondrial numbers per oocyte occurs during adult follicular growth and development, as resting primordial follicles develop to preovulatory maturity. So few are the numbers of oocytes that fertilize and successfully cleave to form an embryo of the new generation, that biologists have long suspected that a competitive constraint lies behind the generational completion of this genetic cycle. I propose that maintaining the integrity of mitochondrial inheritance is such a strong evolutionary imperative that features of ovarian follicular formation, function, and loss could be expected to have been primarily adapted to this special purpose. To extend the hypothesis further, the imperative of maintaining mitochondrial genomic integrity in a population could explain why women normally become sterile a number of years before there is depletion of ovarian follicles and endocrine ovarian failure (i.e. why there is 'an oopause' preceding the menopause). Plausible explanations might also follow for several well-known and puzzling reproductive difficulties, including recurrent miscarriage, unexplained infertility, and persistent failure of IVF embryos to cleave or to implant. Current experimental laboratory manoeuvres that might circumvent mitochondrial shortcomings (such as cytoplasmic transfusion and karyoplast exchange) are examined and possible clinical hazards identified.
Assuntos
Herança Extracromossômica/fisiologia , Células Germinativas/fisiologia , Mutação em Linhagem Germinativa/fisiologia , Mitocôndrias/fisiologia , DNA Mitocondrial/genética , Feminino , Células Germinativas/ultraestrutura , Humanos , MasculinoRESUMO
To a maternally transmitted parasite, male hosts are evolutionary prison cells. This is because passage into the next host generation is only possible via egg cytoplasm and not sperm. However, these parasites have come up with a neat array of evolutionary tricks to make the best of their custodial sentence.
Assuntos
Bactérias/genética , Microsporídios/genética , Processos de Determinação Sexual , Animais , Herança Extracromossômica/genética , Herança Extracromossômica/fisiologia , Feminino , Insetos/parasitologia , Masculino , Partenogênese/fisiologia , Reprodução/fisiologia , Seleção GenéticaRESUMO
Acentric, autonomously replicating extrachromosomal structures called double-minute chromosomes (DMs) frequently mediate oncogene amplification in human tumors. We show that DMs can be removed from the nucleus by a novel micronucleation mechanism that is initiated by budding of the nuclear membrane during S phase. DMs containing c-myc oncogenes in a colon cancer cell line localized to and replicated at the nuclear periphery. Replication inhibitors increased micronucleation; cell synchronization and bromodeoxyuridine-pulse labeling demonstrated de novo formation of buds and micronuclei during S phase. The frequencies of S-phase nuclear budding and micronucleation were increased dramatically in normal human cells by inactivating p53, suggesting that an S-phase function of p53 minimizes the probability of producing the broken chromosome fragments that induce budding and micronucleation. These data have implications for understanding the behavior of acentric DNA in interphase nuclei and for developing chemotherapeutic strategies based on this new mechanism for DM elimination.
Assuntos
Núcleo Celular/genética , DNA de Neoplasias/metabolismo , Herança Extracromossômica/fisiologia , Fase S/genética , Antimetabólitos , Bromodesoxiuridina , Núcleo Celular/patologia , Humanos , Hibridização in Situ Fluorescente , Tumores Neuroendócrinos , Replicon/fisiologia , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/fisiologia , Proteína Supressora de Tumor p53/fisiologiaRESUMO
Actualmente, la genética moderna se considera una disciplina central en el estudio de la variabilidad y la herencia humana; ha permitido el entendimiento de muchas enfermedades de las diferentes áreas médicas y en un futuro se esperan importantes logros. El modelo de herencia mendeliana en la que rasgos dominantes y recesivos se transmiten de acuerdo a la segregación cromosómica es la base del conocimiento de las enfermedades genéticas. Sin embargo, muchos clínicos se encuentran con familias cuya historia genética no se explica fácilmente por este esquema. La genética molecular ha revelado nuevos mecanismos acerca de la herencia humana que permite explicar esta ®herencia no tradicional¼, la cual incluye principalmente: el mosaicismo, herencia mitocondrial, impronta genómica, disomía uniparental y enfermedades por trinucleótidos de repetición
Assuntos
Fenilalanina/deficiência , Fenilalanina/genética , Aberrações Cromossômicas/fisiopatologia , Aberrações Cromossômicas/genética , Heterozigoto , Biologia Molecular/tendências , Triagem de Portadores Genéticos/métodos , Genética Médica , Herança Extracromossômica/fisiologia , Herança Extracromossômica/genéticaRESUMO
We have shown that the extrachromosomal DNA body present in the oocyte nucleus of Creophilus maxillosus contains amplified copies of ribosomal DNA and that multiple nucleoli associated with extrachromosomal DNA body contain ribosomal RNA. In addition, we assessed the level of rDNA amplification in Creophilus oocytes. The amount of DNA in single extra DNA body corresponds to 86% of total nuclear DNA content or 617% of chromosomal DNA content. In Creophilus, there are two phases of transcriptional activity of extrachromosomal rDNA, first in oogonia, and second in growing oocytes, separated by a short period of transcriptional quiescence in the ovary of newly hatched imago. We have described the organization and activity of extra DNA body in RNA synthesis and production of multiple nucleoli in previtellogenic stages of oocyte growth in imaginal ovariole of Creophilus.