Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
1.
Cell ; 186(24): 5308-5327.e25, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37922900

RESUMO

Mammalian oocytes are filled with poorly understood structures called cytoplasmic lattices. First discovered in the 1960s and speculated to correspond to mammalian yolk, ribosomal arrays, or intermediate filaments, their function has remained enigmatic to date. Here, we show that cytoplasmic lattices are sites where oocytes store essential proteins for early embryonic development. Using super-resolution light microscopy and cryoelectron tomography, we show that cytoplasmic lattices are composed of filaments with a high surface area, which contain PADI6 and subcortical maternal complex proteins. The lattices associate with many proteins critical for embryonic development, including proteins that control epigenetic reprogramming of the preimplantation embryo. Loss of cytoplasmic lattices by knocking out PADI6 or the subcortical maternal complex prevents the accumulation of these proteins and results in early embryonic arrest. Our work suggests that cytoplasmic lattices enrich maternally provided proteins to prevent their premature degradation and cellular activity, thereby enabling early mammalian development.


Assuntos
Oócitos , Proteínas , Gravidez , Animais , Feminino , Oócitos/metabolismo , Proteínas/metabolismo , Embrião de Mamíferos/metabolismo , Citoesqueleto , Ribossomos , Desenvolvimento Embrionário , Mamíferos
2.
Bioessays ; 42(7): e1900238, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32302008

RESUMO

The terms "eustress" and "distress" are widely used throughout the scientific literature. As of February 2020, 203 items in the Web of Science show up in a search for "eustress," however, there are almost 16 400 items found in a search for the term "distress." Based on the reasoning in this article, however, it is believed there is no such thing as eustress or distress. The adaptation reaction of an organism under stress is not intrinsically good or bad, and its effect on health or performance depends on a plethora of other interactions of the body with the environment as well as on the history of such interactions. The vagueness of the terms "eustress/distress" has historically led to vast differences in the perception and application of the terms across disciplines. While psychology or sociology perceive eustress as something inextricably linked to positive perception and enhanced cognition, biomedicine perceives eustress as generally associated with better survival, health, or increased longevity, no matter how the event is perceived. In this paper, the authors review the current understanding of the term "eustress" in different fields, discuss possible implications of its misleading use, and suggest that the term may be replaced by "stress" only.


Assuntos
Cognição , Estresse Psicológico , Humanos
3.
Bioessays ; 41(6): e1900014, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31087675

RESUMO

Most contemporary models of disease development consider the interaction between genotype and environment as static. The authors argue that because time is a key factor in genotype-environment interaction, this approach oversimplifies the pathology analysis and may lead to wrong conclusions. In reviewing the field, the authors suggest that the history of genotype-environment interactions plays an important role in the development of diseases and that this history may be analyzed using the phenotype as a proxy. Furthermore, a theoretical and experimental framework is proposed based on the assumption that phenotypes do not change from one to another randomly but are interconnected and follow certain phenotype trajectories. It then follows that analysis of such phenotype trajectories might be useful to predict the future phenotypes including the onset of disease. In addition, an analysis of phenotype trajectories can be subsequently used to choose better control subjects in comparative studies reducing noise and bias in studies investigating disease mechanisms.


Assuntos
Doença/genética , Interação Gene-Ambiente , Genótipo , Modelos Genéticos , Patologia/métodos , Envelhecimento/genética , Viés , Métodos Epidemiológicos , Predisposição Genética para Doença , Variação Genética , Humanos , Tempo
4.
J Cell Sci ; 130(4): 712-724, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28062848

RESUMO

Dorsal closure of the Drosophila embryonic epithelium provides an excellent model system for the in vivo analysis of molecular mechanisms regulating cytoskeletal rearrangements. In this study, we investigated the function of the Drosophila spectraplakin Short stop (Shot), a conserved cytoskeletal structural protein, during closure of the dorsal embryonic epithelium. We show that Shot is essential for the efficient final zippering of the opposing epithelial margins. By using isoform-specific mutant alleles and genetic rescue experiments with truncated Shot variants, we demonstrate that Shot functions as an actin-microtubule cross-linker in mediating zippering. At the leading edge of epithelial cells, Shot regulates protrusion dynamics by promoting filopodia formation. Fluorescence recovery after photobleaching (FRAP) analysis and in vivo imaging of microtubule growth revealed that Shot stabilizes dynamic microtubules. The actin- and microtubule-binding activities of Shot are simultaneously required in the same molecule, indicating that Shot is engaged as a physical crosslinker in this process. We propose that Shot-mediated interactions between microtubules and actin filaments facilitate filopodia formation, which promotes zippering by initiating contact between opposing epithelial cells.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Células Epiteliais/metabolismo , Proteínas dos Microfilamentos/metabolismo , Microtúbulos/metabolismo , Morfogênese , Actinas/metabolismo , Animais , Proteínas de Drosophila/química , Drosophila melanogaster/embriologia , Embrião não Mamífero/metabolismo , Células Epiteliais/citologia , Proteínas de Fluorescência Verde/metabolismo , Proteínas dos Microfilamentos/química , Mutação/genética , Domínios Proteicos , Pseudópodes/metabolismo
5.
PLoS Comput Biol ; 14(11): e1006588, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30439934

RESUMO

Cytoplasmic flows are an ubiquitous feature of biological systems, in particular in large cells, such as oocytes and eggs in early animal development. Here we show that cytoplasmic flows in starfish oocytes, which can be imaged well with transmission light microscopy, are fully determined by the cortical dynamics during surface contraction waves. We first show that the dynamics of the oocyte surface is highly symmetric around the animal-vegetal axis. We then mathematically solve the Stokes equation for flows inside a deforming sphere using the measured surface displacements as boundary conditions. Our theoretical predictions agree very well with the intracellular flows quantified by particle image velocimetry, proving that during this stage the starfish cytoplasm behaves as a simple Newtonian fluid on the micrometer scale. We calculate the pressure field inside the oocyte and find that its gradient is too small as to explain polar body extrusion, in contrast to earlier suggestions. Myosin II inhibition by blebbistatin confirms this conclusion, because it diminishes cell shape changes and hydrodynamic flow, but does not abolish polar body formation.


Assuntos
Citoplasma/fisiologia , Oócitos/citologia , Estrelas-do-Mar/fisiologia , Actinas/química , Algoritmos , Animais , Citoplasma/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/química , Imageamento Tridimensional , Modelos Teóricos , Miosina Tipo II/metabolismo , Distribuição Normal , Corpos Polares , Rotação , Água do Mar , Propriedades de Superfície
6.
Biol Lett ; 15(6): 20190091, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31164060

RESUMO

Many studies during the past 50 years have found an association between father absence and earlier menarche. In connection with these findings, several evolutionary theories assume that father absence is a causal factor accelerating reproductive development. However, a recent study analysing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) found that father absence does not predict age at menarche when adjusted for sibling relatedness. In this study, we have replicated these results in the Czech section of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC), which used the same questionnaires as ALSPAC to study a geographically distinct population. Our results support the conclusion that sibling relatedness rather than father absence predicts age at menarche. Furthermore, our results show that age at menarche in 1990s UK and Czech cohorts is very similar despite socioeconomic differences between the two countries.


Assuntos
Pai , Menarca , Fatores Etários , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Gravidez , Irmãos
7.
Biogerontology ; 18(4): 693-709, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28013399

RESUMO

For decades, a vast majority of biogerontologists assumed that aging is not and cannot be an adaptation. In recent years, however, several authors opposed this predominant view and repeatedly suggested that not only is aging an adaptation but that it is the result of a specific aging program. This issue almost instantaneously became somewhat controversial and many important authors produced substantial works refuting the notion of the aging program. In this article we review the current state of the debate and list the most important arguments proposed by both sides. Furthermore, although classical interpretations of the evolution of aging are in sharp contrast with the idea of programmed aging, we suggest that the truth might in fact very well lie somewhere in between. We also propose our own interpretation which states that although aging is in essence inevitable and results from damage accumulation rather than from a specific program, the actual rate of aging in nature may still be adaptive to some extent.


Assuntos
Adaptação Fisiológica , Envelhecimento/fisiologia , Evolução Biológica , Fatores Etários , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Regulação da Expressão Gênica , Nível de Saúde , Humanos , Modelos Biológicos , Dinâmica Populacional
8.
Chromosoma ; 124(4): 481-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25944357

RESUMO

Actin's presence in the nucleus is a subject that has ignited a lot of controversy in the past. With our review, we attempt to reach out not only to the specialists but also to a broader audience that might be skeptical in light of the controversies. We take a rather conservative approach to build an argument that recent studies provide multiple independent lines of evidence substantiating actin's diverse nuclear functions, especially in its monomeric state. We then particularly focus on how the concentration of monomeric actin, and potentially of specific polymerized forms of actin, can be used by the cell as indicators of cellular state and how this information can be transduced into the nucleus by transcriptional regulators, eliciting a response. We also provide examples that in specific cell types and specific physiological conditions, actin is functional in the nucleus in its polymeric form. However, we also discuss that in many instances, the presence of actin regulators in the nucleus, which is often seen as proof of their function within this compartment, may simply reflect an additional means of their regulation by compartmentalization.


Assuntos
Actinas/fisiologia , Núcleo Celular/metabolismo , Animais , Eucariotos , Humanos
9.
Nat Commun ; 14(1): 7564, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985670

RESUMO

Even slight imbalance between the growth rate of different organs can accumulate to a large deviation from their appropriate size during development. Here, we use live imaging of the pharynx of C. elegans to ask if and how organ size scaling nevertheless remains uniform among individuals. Growth trajectories of hundreds of individuals reveal that pharynxes grow by a near constant volume per larval stage that is independent of their initial size, such that undersized pharynxes catch-up in size during development. Tissue-specific depletion of RAGA-1, an activator of mTOR and growth, shows that maintaining correct pharynx-to-body size proportions involves a bi-directional coupling between pharynx size and body growth. In simulations, this coupling cannot be explained by limitation of food uptake alone, and genetic experiments reveal an involvement of the mechanotransducing transcriptional co-regulator yap-1. Our data suggests that mechanotransduction coordinates pharynx growth with other tissues, ensuring body plan uniformity among individuals.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Humanos , Animais , Caenorhabditis elegans/genética , Faringe/metabolismo , Mecanotransdução Celular , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Sinalização YAP
10.
Psychoneuroendocrinology ; 158: 106382, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37708823

RESUMO

Many animals react to threatening stimuli such as a predator attacks by freezing. However, little experimental research investigated freeze response in humans. Here, we have employed practices commonly used in self-defense training to create two unique scenarios simulating armed physical threat. Sixty healthy men volunteers divided into three groups of twenty (untrained, trained but unexperienced, trained and experienced) underwent these scenarios accompanied by measurement of biochemical, physiological, and psychological markers of stress. Our results show that untrained individuals exhibit stronger freezing reactions, while highly skilled participants display the lowest propensity for freezing, especially in high-intensity scenarios. Moreover, the study shows variations in anxiety levels and selected biomarkers, with cortisol and osteocalcin showing different patterns in low and high-intensity scenarios, and suggests a complex interplay between these factors, electrodermal activity, and stress perception.


Assuntos
Fatores Biológicos , Autoimagem , Masculino , Animais , Humanos , Hidrocortisona , Estresse Psicológico/psicologia
11.
Biophys J ; 103(3): 616-626, 2012 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-22947879

RESUMO

Quantitative tracking of particle motion using live-cell imaging is a powerful approach to understanding the mechanism of transport of biological molecules, organelles, and cells. However, inferring complex stochastic motion models from single-particle trajectories in an objective manner is nontrivial due to noise from sampling limitations and biological heterogeneity. Here, we present a systematic Bayesian approach to multiple-hypothesis testing of a general set of competing motion models based on particle mean-square displacements that automatically classifies particle motion, properly accounting for sampling limitations and correlated noise while appropriately penalizing model complexity according to Occam's Razor to avoid over-fitting. We test the procedure rigorously using simulated trajectories for which the underlying physical process is known, demonstrating that it chooses the simplest physical model that explains the observed data. Further, we show that computed model probabilities provide a reliability test for the downstream biological interpretation of associated parameter values. We subsequently illustrate the broad utility of the approach by applying it to disparate biological systems including experimental particle trajectories from chromosomes, kinetochores, and membrane receptors undergoing a variety of complex motions. This automated and objective Bayesian framework easily scales to large numbers of particle trajectories, making it ideal for classifying the complex motion of large numbers of single molecules and cells from high-throughput screens, as well as single-cell-, tissue-, and organism-level studies.


Assuntos
Modelos Biológicos , Movimento (Física) , Teorema de Bayes , Sobrevivência Celular , Difusão , Movimento
12.
Sci Rep ; 12(1): 20403, 2022 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-36437294

RESUMO

Genetic drift is a basic evolutionary principle describing random changes in allelic frequencies, with far-reaching consequences in various topics ranging from species conservation efforts to speciation. The conventional approach assumes that genetic drift has the same effect on all populations undergoing the same changes in size, regardless of different non-reproductive behaviors and history of the populations. However, here we reason that processes leading to a systematic increase of individuals` chances of survival, such as learning or immunological memory, can mitigate loss of genetic diversity caused by genetic drift even if the overall mortality rate in the population does not change. We further test this notion in an agent-based model with overlapping generations, monitoring allele numbers in a population of prey, either able or not able to learn from successfully escaping predators' attacks. Importantly, both these populations start with the same effective size and have the same and constant overall mortality rates. Our results demonstrate that even under these conditions, learning can mitigate loss of genetic diversity caused by drift, by creating a pool of harder-to-die individuals that protect alleles they carry from extinction. Furthermore, this effect holds regardless if the population is haploid or diploid or whether it reproduces sexually or asexually. These findings may be of importance not only for basic evolutionary theory but also for other fields using the concept of genetic drift.


Assuntos
Evolução Biológica , Deriva Genética , Humanos , Frequência do Gene , Alelos , Diploide
13.
Sci Rep ; 12(1): 9583, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688908

RESUMO

TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved for cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous, but mainly viral pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. Increase in TACSTD2 expression may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.


Assuntos
Antígenos de Neoplasias , Moléculas de Adesão Celular , Animais , Antígenos de Neoplasias/metabolismo , Moléculas de Adesão Celular/metabolismo , Células Epiteliais/metabolismo , Pulmão/metabolismo , Regulação para Cima
14.
J Clin Endocrinol Metab ; 107(3): 755-775, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-34669916

RESUMO

CONTEXT: Adipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities. OBJECTIVE: Here we aim to compare the proteomic profiles of mature adipocytes from different depots. METHODS: Abdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data. RESULTS: We identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. CONCLUSION: Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity.


Assuntos
Adipócitos/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade Mórbida/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adulto , Cirurgia Bariátrica , Feminino , Redes Reguladoras de Genes , Humanos , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/patologia , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Omento/citologia , Omento/metabolismo , Omento/patologia , Omento/cirurgia , Proteômica , Gordura Subcutânea Abdominal/citologia , Gordura Subcutânea Abdominal/patologia
15.
Curr Opin Cell Biol ; 15(1): 88-95, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12517709

RESUMO

We have recently gained new insight into the mechanisms involved in nuclear envelope breakdown, the irreversible step that commits a cell to the M phase. Results from mammalian cell and starfish oocyte studies suggest that mechanical forces of the cytoskeleton, as well as biochemical disassembly of nuclear envelope protein complexes, play important roles in this process.


Assuntos
Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Membrana Nuclear/metabolismo , Oócitos/metabolismo , Animais , Tamanho Celular/fisiologia , Fertilização/fisiologia , Humanos , Modelos Biológicos , Membrana Nuclear/ultraestrutura , Oócitos/ultraestrutura
16.
Curr Opin Cell Biol ; 16(3): 314-21, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15145357

RESUMO

In eukaryotic cells, all macromolecules that traffic between the nucleus and the cytoplasm cross the double nuclear membrane through nuclear pore complexes (NPCs). NPCs are elaborate gateways that allow efficient, yet selective, translocation of many different macromolecules. Their protein composition has been elucidated, but how exactly these nucleoporins come together to form the pore is largely unknown. Recent data suggest that NPCs are composed of an extremely stable scaffold on which more dynamic, exchangeable parts are assembled. These could be targets for molecular rearrangements that change nuclear pore transport properties and, ultimately, the state of the cell.


Assuntos
Ciclo Celular/fisiologia , Poro Nuclear/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Núcleo Celular/metabolismo , Humanos , Membrana Nuclear/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo
17.
Nature ; 436(7052): 812-8, 2005 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-16015286

RESUMO

Chromosome capture by microtubules is widely accepted as the universal mechanism of spindle assembly in dividing cells. However, the observed length of spindle microtubules and computer simulations of spindle assembly predict that chromosome capture is efficient in small cells, but may fail in cells with large nuclear volumes such as animal oocytes. Here we investigate chromosome congression during the first meiotic division in starfish oocytes. We show that microtubules are not sufficient for capturing chromosomes. Instead, chromosome congression requires actin polymerization. After nuclear envelope breakdown, we observe the formation of a filamentous actin mesh in the nuclear region, and find that contraction of this network delivers chromosomes to the microtubule spindle. We show that this mechanism is essential for preventing chromosome loss and aneuploidy of the egg--a leading cause of pregnancy loss and birth defects in humans.


Assuntos
Actinas/metabolismo , Núcleo Celular/metabolismo , Segregação de Cromossomos , Cromossomos/fisiologia , Meiose , Oócitos/metabolismo , Actinas/química , Animais , Transporte Biológico/efeitos dos fármacos , Biopolímeros/química , Biopolímeros/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Núcleo Celular/genética , Segregação de Cromossomos/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Microscopia Confocal , Microtúbulos/metabolismo , Nocodazol/farmacologia , Oócitos/citologia , Especificidade da Espécie , Estrelas-do-Mar , Tiazóis/farmacologia , Tiazolidinas
18.
BMC Ecol Evol ; 21(1): 87, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34000997

RESUMO

BACKGROUND: The pace of aging varies considerably in nature. The best-known explanation of the evolution of specific rates of aging is the Williams' hypothesis suggesting that the aging rate should correlate with the level of extrinsic mortality. However, the current evidence is inconclusive with various examples where the Williams' hypothesis seems to be correct and where it doesn't. Here we explore the relationship between extrinsic mortality and aging rate by developing a simulation model of the evolution of aging rate in prey subject to predation. RESULTS: Our results suggest that more intense predation leads to the evolution of faster pace of aging in prey. However, this effect slowly vanishes when the predator diet breadth is allowed to evolve, too. Furthermore, in our model, the evolution of a specific aging rate is driven mainly by a single parameter, the strength of a trade-off between aging and fecundity. Indeed, in the absence of this trade-off the evolutionary impacts of predation on the prey aging rate appear random. CONCLUSIONS: We show that the William's hypothesis appears valid when there is a trade-off between aging and fecundity and predators and prey do not coevolve. However, we also show that when the prey and predators coevolve or if there is no trade-off between aging and fecundity the William`s hypothesis is no longer applicable.


Assuntos
Modelos Biológicos , Comportamento Predatório , Envelhecimento , Animais , Simulação por Computador
19.
Sci Rep ; 11(1): 17327, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462454

RESUMO

All homoiothermic organisms are capable of maintaining a stable body temperature using various negative feedback mechanisms. However, current models cannot satisfactorily describe the thermal adaptation of homoiothermic living systems in a physiologically meaningful way. Previously, we introduced stress entropic load, a novel variable designed to quantify adaptation costs, i.e. the stress of the organism, using a thermodynamic approach. In this study, we use stress entropic load as a starting point for the construction of a novel dynamical model of human thermoregulation. This model exhibits bi-stable mechanisms, a physiologically plausible features which has thus far not been demonstrated using a mathematical model. This finding allows us to predict critical points at which a living system, in this case a human body, may proceed towards two stabilities, only one of which is compatible with being alive. In the future, this may allow us to quantify not only the direction but rather the extent of therapeutic intervention in critical care patients.


Assuntos
Regulação da Temperatura Corporal , Temperatura Corporal , Homeostase , Aclimatação , Adaptação Fisiológica , Animais , Humanos , Masculino , Modelos Biológicos , Modelos Teóricos , Termodinâmica
20.
Curr Biol ; 17(7): 630-6, 2007 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-17349791

RESUMO

Sister chromatid cohesion depends on cohesin [1-3]. Cohesin associates with chromatin dynamically throughout interphase [4]. During DNA replication, cohesin establishes cohesion [5], and this process coincides with the generation of a cohesin subpopulation that is more stably bound to chromatin [4]. In mitosis, cohesin is removed from chromosomes, enabling sister chromatid separation [6]. How cohesin associates with chromatin and establishes cohesion is poorly understood. By searching for proteins that are associated with chromatin-bound cohesin, we have identified sororin, a protein that was known to be required for cohesion [7]. To obtain further insight into sororin's function, we have addressed when during the cell cycle sororin is required for cohesion. We show that sororin is dispensable for the association of cohesin with chromatin but that sororin is essential for proper cohesion during G2 phase. Like cohesin, sororin is also needed for efficient repair of DNA double-strand breaks in G2. Finally, sororin is required for the presence of normal amounts of the stably chromatin-bound cohesin population in G2. Our data indicate that sororin interacts with chromatin-bound cohesin and functions during the establishment or maintenance of cohesion in S or G2 phase, respectively.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Cromátides/fisiologia , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Interfase , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/química , Cromatina/química , Proteínas Cromossômicas não Histona/química , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Fase G2 , Células HeLa , Humanos , Immunoblotting , Proteínas Nucleares/química , Coesinas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA