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1.
Plants (Basel) ; 13(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611519

RESUMEN

Olive (Olea europaea L.) is one of the major oil fruit tree crops worldwide. However, the mechanisms underlying olive fruit growth remain poorly understood. Here, we examine questions regarding the interaction of endoreduplication, cell division, and cell expansion with olive fruit growth in relation to the final fruit size by measuring fruit diameter, pericarp thickness, cell area, and ploidy level during fruit ontogeny in three olive cultivars with different fruit sizes. The results demonstrate that differences in the fruit size are related to the maximum growth rate between olive cultivars during early fruit growth, about 50 days post-anthesis (DPA). Differences in fruit weight between olive cultivars were found from 35 DPA, while the distinctive fruit shape became detectable from 21 DPA, even though the increase in pericarp thickness became detectable from 7 DPA in the three cultivars. During early fruit growth, intense mitotic activity appeared during the first 21 DPA in the fruit, whereas the highest cell expansion rates occurred from 28 to 42 DPA during this phase, suggesting that olive fruit cell number is determined from 28 DPA in the three cultivars. Moreover, olive fruit of the large-fruited cultivars was enlarged due to relatively higher cell division and expansion rates compared with the small-fruited cultivar. The ploidy level of olive fruit pericarp between early and late growth was different, but similar among olive cultivars, revealing that ploidy levels are not associated with cell size, in terms of different 8C levels during olive fruit growth. In the three olive cultivars, the maximum endoreduplication level (8C) occurred just before strong cell expansion during early fruit growth in fruit pericarp, whereas the cell expansion during late fruit growth occurred without preceding endoreduplication. We conclude that the basis for fruit size differences between olive cultivars is determined mainly by different cell division and expansion rates during the early fruit growth phase. These data provide new findings on the contribution of fruit ploidy and cell size to fruit size in olive and ultimately on the control of olive fruit development.

2.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36674474

RESUMEN

In the olive (Olea europaea L.), an economically leading oil crop worldwide, fruit size and yield are determined by the early stages of fruit development. However, few detailed analyses of this stage of fruit development are available. This study offers an extensive characterization of the various processes involved in early olive fruit growth (cell division, cell cycle regulation, and cell expansion). For this, cytological, hormonal, and transcriptional changes characterizing the phases of early fruit development were analyzed in olive fruit of the cv. 'Picual'. First, the surface area and mitotic activity (by flow cytometry) of fruit cells were investigated during early olive fruit development, from 0 to 42 days post-anthesis (DPA). The results demonstrate that the cell division phase extends up to 21 DPA, during which the maximal proportion of 4C cells in olive fruits was reached at 14 DPA, indicating that intensive cell division was activated in olive fruits at that time. Subsequently, fruit cell expansion lasted as long as 3 weeks more before endocarp lignification. Finally, the molecular mechanisms controlling the early fruit development were investigated by analyzing the transcriptome of olive flowers at anthesis (fruit set) as well as olive fruits at 14 DPA (cell division phase) and at 28 DPA (cell expansion phase). Sequential induction of the cell cycle regulating genes is associated with the upregulation of genes involved in cell wall remodeling and ion fluxes, and with a shift in plant hormone metabolism and signaling genes during early olive fruit development. This occurs together with transcriptional activity of subtilisin-like protease proteins together with transcription factors potentially involved in early fruit growth signaling. This gene expression profile, together with hormonal regulators, offers new insights for understanding the processes that regulate cell division and expansion, and ultimately fruit yield and olive size.


Asunto(s)
Olea , Transcriptoma , Olea/metabolismo , Frutas/metabolismo , Factores de Transcripción/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo
3.
Plants (Basel) ; 11(5)2022 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-35270158

RESUMEN

The role of melatonin during the growth and ripening of apple fruit was studied using local varieties. The evolution of the growth and ripening parameters, including fruit size and weight, firmness, color change, sugar content, and ethylene production, was different in the five varieties studied, with yellow apples (Reineta and Golden) initiating the ripening process earlier than reddish ones (Teórica, Sanroqueña, and Caguleira). Changes in the melatonin and melatonin isomer 2 contents during growth and ripening were studied in Golden apples, as was the effect of the melatonin treatment (500 µM, day 124 post-anthesis) on the apple tree. Melatonin content varied greatly, with higher value in the skin than in the flesh. In the skin, melatonin increased at day 132 post-anthesis, when ethylene synthesis started. In the flesh, melatonin levels were high at the beginning of the growth phase and at the end of ripening. Melatonin isomer 2 was also higher once the ripening started and when ethylene began to increase. The melatonin treatment significantly advanced the ethylene production and increased the fruit size, weight, sugar content, and firmness. The data suggest that melatonin stimulates fruit ripening through the induction of ethylene synthesis, while melatonin treatments before ripening improve the final fruit quality.

4.
Int J Mol Sci ; 21(14)2020 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-32650402

RESUMEN

Fruit ripening and abscission are the results of the cell wall modification concerning different components of the signaling network. However, molecular-genetic information on the cross-talk between ripe fruit and their abscission zone (AZ) remains limited. In this study, we investigated transcriptional and hormonal changes in olive (Olea europaea L. cv Picual) pericarp and AZ tissues of fruit at the last stage of ripening, when fruit abscission occurs, to establish distinct tissue-specific expression patterns related to cell-wall modification, plant-hormone, and vesicle trafficking in combination with data on hormonal content. In this case, transcriptome profiling reveals that gene encoding members of the α-galactosidase and ß-hexosaminidase families associated with up-regulation of RabB, RabD, and RabH classes of Rab-GTPases were exclusively transcribed in ripe fruit enriched in ABA, whereas genes of the arabinogalactan protein, laccase, lyase, endo-ß-mannanase, ramnose synthase, and xyloglucan endotransglucosylase/hydrolase families associated with up-regulation of RabC, RabE, and RabG classes of Rab-GTPases were exclusively transcribed in AZ-enriched mainly in JA, which provide the first insights into the functional divergences among these protein families. The enrichment of these protein families in different tissues in combination with data on transcript abundance offer a tenable set of key genes of the regulatory network between olive fruit tissues in late development.


Asunto(s)
Frutas/genética , Frutas/metabolismo , Olea/genética , Olea/metabolismo , Reguladores del Crecimiento de las Plantas/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Transcriptoma/genética , Pared Celular/genética , Pared Celular/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas/genética , Redes Reguladoras de Genes/genética , Transducción de Señal/genética , alfa-Galactosidasa/genética , alfa-Galactosidasa/metabolismo , beta-N-Acetilhexosaminidasas/genética , beta-N-Acetilhexosaminidasas/metabolismo
5.
Plant Cell Physiol ; 61(4): 814-825, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32016408

RESUMEN

Cell wall modification is integral to many plant developmental processes where cells need to separate, such as abscission. However, changes in cell wall composition during natural fruit abscission are poorly understood. In olive (Olea europaea L.), some cultivars such as 'Picual' undergo massive natural fruit abscission after fruit ripening. This study investigates the differences in cell wall polysaccharide composition and the localization of pectins and arabinogalactan protein (AGP) in the abscission zone (AZ) during cell separation to understand fruit abscission control in 'Picual' olive. To this end, immunogold labeling employing a suite of monoclonal antibodies to cell wall components (JIM13, LM5, LM6, LM19 and LM20) was investigated in olive fruit AZ. Cell wall polysaccharide extraction revealed that the AZ cell separation is related to the de-esterification and degradation of pectic polysaccharides. Moreover, ultrastructural localization showed that both esterified and unesterified homogalacturonans (HGs) localize mainly in the AZ cell walls, including the middle lamella and tricellular junction zones. Our results indicate that unesterified HGs are likely to contribute to cell separation in the olive fruit AZ. Similarly, immunogold labeling demonstrated a decrease in both galactose-rich and arabinose-rich pectins in AZ cell walls during ripe fruit abscission. In addition, AGPs were localized in the cell wall, plasma membrane and cytoplasm of AZ cells with lower levels of AGPs during ripe fruit abscission. This detailed temporal profile of the cell wall polysaccharide composition, and the pectins and AGP immunolocalization in the olive fruit AZ, offers new insights into cell wall remodeling during ripe fruit abscission.


Asunto(s)
Pared Celular/ultraestructura , Frutas/química , Galactanos/ultraestructura , Mucoproteínas/ultraestructura , Olea/química , Pectinas/ultraestructura , Arabinosa/metabolismo , Esterificación , Galactosa/metabolismo , Proteínas de Plantas/ultraestructura , Polisacáridos/ultraestructura
6.
J Plant Physiol ; 231: 383-392, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30390495

RESUMEN

Sphingolipids are abundant membrane components and signalling molecules in various aspects of plant development. However, the role of sphingolipids in early fleshy-fruit growth has rarely been investigated. In this study, we first investigated the temporal changes in sphingolipid long-chain base (LCB) content, composition, and gene expression that occurred during flower opening and early fruit development in olive (Olea europaea L. cv Picual). Moreover, the interaction between sphingolipid and the plant hormone, brassinosteroid (BR), during the early fruit development was also explored. For this, BR levels were manipulated through the application of exogenous BRs (24-epibrassinolide, EBR) or a BR biosynthesis inhibitor (brassinazole, Brz) and their effects on early fruit development, sphingolipid LCB content, and gene expression were examined in olive fruit at 14 days post-anthesis (DPA). We here show that sphingolipid with C-4 hydroxylation and Δ8 desaturation with a preference for (E)-isomer formation are quantitatively the most important sphingolipids in olive reproductive organs. In this work, the total LCB amount significantly decreased at the anthesis stage, but olive sphingosine-1-phosphate lyase (OeSPL) gene was expressed exclusively in flower and upregulated during the anthesis, revealing an association with the d18:1(8E) accumulation. However, the LCB content increased in parallel with the upregulation of the expression of genes for key sphingolipid biosynthetic and LCB modification enzymes during early fruit development in olive. Likewise, we found that EBR exogenously applied to olive trees significantly stimulated the fruit growth rate whereas Brz inhibited fruit growth rate after 7 and 14 days of treatment. In addition, this inhibitory effect could be counteracted by the application of EBR. The promotion of early fruit growth was accompanied by the down-regulation of sphingolipid LCB content and gene expression in olive fruit, whereas Brz application raised levels of sphingolipid LCB content and gene expression in olive fruit after 7 and 14 days of treatment. Thus, our data indicate that endogenous sphingolipid LCB and gene-expression levels are intricately controlled during early fruit development and also suggest a possible link between BR, the sphingolipid content/gene expression, and early fruit development in olive.


Asunto(s)
Brasinoesteroides/metabolismo , Frutas/metabolismo , Olea/metabolismo , Esfingolípidos/metabolismo , Frutas/crecimiento & desarrollo , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Olea/crecimiento & desarrollo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcriptoma
7.
Front Plant Sci ; 9: 28, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29434611

RESUMEN

Plant sphingolipids are involved in the building of the matrix of cell membranes and in signaling pathways of physiological processes and environmental responses. However, information regarding their role in fruit development and ripening, a plant-specific process, is unknown. The present study seeks to determine whether and, if so, how sphingolipids are involved in fleshy-fruit development and ripening in an oil-crop species such as olive (Olea europaea L. cv. Picual). Here, in the plasma-membranes of live protoplasts, we used fluorescence to examine various specific lipophilic stains in sphingolipid-enriched regions and investigated the composition of the sphingolipid long-chain bases (LCBs) as well as the expression patterns of sphingolipid-related genes, OeSPT, OeSPHK, OeACER, and OeGlcCerase, during olive-fruit development and ripening. The results demonstrate increased sphingolipid content and vesicle trafficking in olive-fruit protoplasts at the onset of ripening. Moreover, the concentration of LCB [t18:1(8Z), t18:1 (8E), t18:0, d18:2 (4E/8Z), d18:2 (4E/8E), d18:1(4E), and 1,4-anhydro-t18:1(8E)] increases during fruit development to reach a maximum at the onset of ripening, although these molecular species decreased during fruit ripening. On the other hand, OeSPT, OeSPHK, and OeGlcCerase were expressed differentially during fruit development and ripening, whereas OeACER gene expression was detected only at the fully ripe stage. The results provide novel data about sphingolipid distribution, content, and biosynthesis/turnover gene transcripts during fleshy-fruit ripening, indicating that all are highly regulated in a developmental manner.

8.
Prog. obstet. ginecol. (Ed. impr.) ; 60(6): 579-581, nov.-dic. 2017. tab
Artículo en Español | IBECS | ID: ibc-171146

RESUMEN

El acretismo placentario es una importante causa de morbimortalidad materna. El tratamiento clásico de la placenta ácreta es la histerectomía tras la extracción fetal, sin embargo, el manejo conservador es una opción en pacientes con deseos genésicos (AU)


Placenta accreta is a major cause of maternal morbidity and mortality. The classic treatment of placenta accrete is hysterectomy after fetal extraction, however, conservative management is an option in patients with full reproductive desires (AU)


Asunto(s)
Humanos , Femenino , Embarazo , Adolescente , Placenta Accreta/cirugía , Histerectomía , Preservación de la Fertilidad/métodos , Tratamiento Conservador/métodos , Diagnóstico Prenatal , Indicadores de Morbimortalidad , Factores de Riesgo , Retención de la Placenta/cirugía
9.
Prog. obstet. ginecol. (Ed. impr.) ; 60(6): 594-596, nov.-dic. 2017.
Artículo en Español | IBECS | ID: ibc-171149

RESUMEN

El cáncer de mama gestacional, o el cáncer de mama asociado al embarazo se define como aquel que se diagnostica durante el embarazo, el primer año postparto o en cualquier momento durante la lactancia, su incidencia está entre el 0,2% y el 2,6%, pero esta cifra va en aumento en la medida en que la mujer retrasa la maternidad. Predominantemente son tumores pobremente diferenciados y se diagnostican en estadíos avanzados, particularmente cuando esto ocurre durante la lactancia. El tratamiento debe de tener intención curativa, y no debe retrasarse con motivo de la gestación. Los estudios sugieren que es seguro administrar algunos agentes quimioterápicos, sobre todo cuando se inician después del primer trimestre de la gestación, y que en la mayoría de las ocasiones los embarazos acaban con un recién nacido vivo con bajas tasas de morbilidad y mortalidad (1). Estudios recientes han evaluado específicamente los resultados en mujeres diagnosticadas de cáncer de mama durante la gestación y han demostrado que esta no tiene un impacto negativo en la supervivencia (2,3) (AU)


Gestational or pregnancy-associated breast cancer is defined as breast cancer that is diagnosed during pregnancy, in the first postpartum year, or any time during lantation. The incidence of pregnancy-associated breast cancer is between 0.2% and 2.6% and is currently increasing due to delayed childbearing. It´s predominantly poorly differenciated and diagnosed at an advanced stage, particlarly those diagnosed in lactating women. The treatmen should be approached with curative intent, and it should not be unnecessarily delayed because of pregnancy. The data suggest it is safe to administer many agents used in the treatmen of breast cancer during pregnancy when initiated after the first trimester, and that the majority of pregnancies result in live births with low related morbidity in the newborns (1). Contemporrary studies that specifically evaluated the outcomes of women diagnosed with breast cancer during pregnancy have consistently shown that there is no negative impact on survival (2,3) (AU)


Asunto(s)
Humanos , Femenino , Embarazo , Adulto , Neoplasias de la Mama/complicaciones , Complicaciones Neoplásicas del Embarazo , Terapia Neoadyuvante/métodos , Antineoplásicos/uso terapéutico , Resultado del Embarazo , Mastectomía Radical
10.
J Am Coll Cardiol ; 67(21): 2467-76, 2016 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-27230041

RESUMEN

BACKGROUND: Leucocyte telomere length (LTL) shortening is associated with cardiovascular ischemic events and mortality in humans, but data on its association with subclinical atherosclerosis are scarce. Whether the incidence and severity of subclinical atherosclerosis are associated with the abundance of critically short telomeres, a major trigger of cellular senescence, remains unknown. OBJECTIVES: The authors conducted a cross-sectional exploration of the association between subclinical atherosclerosis burden and both average LTL and the abundance of short telomeres (%LTL<3 kb). METHODS: Telomere length was assessed by high-throughput quantitative fluorescence in situ hybridization in circulating leukocytes from 1,459 volunteers without established cardiovascular disease (58% men, 40 to 54 years of age) from the PESA (Progression of Early Subclinical Atherosclerosis) study. Subclinical atherosclerosis was evaluated by coronary artery calcium scan and 2-dimensional/3-dimensional ultrasound in different aortic territories. Statistical significance of differences among multiple covariates was assessed with linear regression models. Independent associations of telomere parameters with plaque presence were evaluated using general linear models. RESULTS: In men and women, age was inversely associated with LTL (Pearson's r = -0.127, p < 0.001) and directly with %LTL<3 kb (Pearson's r = 0.085; p = 0.001). Short LTL reached statistical significance as a determinant of total and femoral plaque in men, but not in women. However, this association was not sustained after adjustment for age or additional adjustment for cardiovascular risk factors. No significant independent association was found between %LTL<3 kb and plaque burden. Serum-oxidized low-density lipoprotein levels were directly associated with %LTL<3 kb in men (p = 0.008) and women (p < 0.001). CONCLUSIONS: In a cross-sectional study of a middle-aged population, average LTL and short telomere load are not significant independent determinants of subclinical atherosclerosis. Longitudinal follow-up of PESA participants will assess long-term associations between telomere length and progression of subclinical atherosclerosis.


Asunto(s)
Aterosclerosis/genética , Leucocitos/metabolismo , Acortamiento del Telómero , Telómero , Adulto , Factores de Edad , Aterosclerosis/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/metabolismo , Estudios Transversales , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/metabolismo , Humanos , Hibridación Fluorescente in Situ , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/genética , Ultrasonografía
11.
Nat Commun ; 6: 8487, 2015 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-26511661

RESUMEN

The cycling properties of mammary stem and progenitor cells is not well understood. To determine the division properties of these cells, we administered synthetic nucleosides for varying periods of time to mice at different stages of postnatal development and monitored the rate of uptake of these nucleosides in the different mammary cell compartments. Here we show that most cell division in the adult virgin gland is restricted to the oestrogen receptor-expressing luminal cell lineage. Our data also demonstrate that the oestrogen receptor-expressing, milk and basal cell subpopulations have telomere lengths and cell division kinetics that are not compatible with these cells being hierarchically organized; instead, our data indicate that in the adult homeostatic gland, each cell type is largely maintained by its own restricted progenitors. We also observe that transplantable stem cells are largely quiescent during oestrus, but are cycling during dioestrus when progesterone levels are high.


Asunto(s)
Autorrenovación de las Células , Glándulas Mamarias Animales/crecimiento & desarrollo , Células Madre/citología , Animales , Femenino , Cinética , Glándulas Mamarias Animales/química , Glándulas Mamarias Animales/citología , Glándulas Mamarias Animales/metabolismo , Ratones , Ratones Endogámicos C57BL , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Células Madre/química , Células Madre/metabolismo
12.
Nat Commun ; 6: 7505, 2015 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-26106036

RESUMEN

Although BRCA1 function is essential for maintaining genomic integrity in all cell types, it is unclear why increased risk of cancer in individuals harbouring deleterious mutations in BRCA1 is restricted to only a select few tissues. Here we show that human mammary epithelial cells (HMECs) from BRCA1-mutation carriers (BRCA1(mut/+)) exhibit increased genomic instability and rapid telomere erosion in the absence of tumour-suppressor loss. Furthermore, we uncover a novel form of haploinsufficiency-induced senescence (HIS) specific to epithelial cells, which is triggered by pRb pathway activation rather than p53 induction. HIS and telomere erosion in HMECs correlate with misregulation of SIRT1 leading to increased levels of acetylated pRb as well as acetylated H4K16 both globally and at telomeric regions. These results identify a novel form of cellular senescence and provide a potential molecular basis for the rapid cell- and tissue- specific predisposition of breast cancer development associated with BRCA1 haploinsufficiency.


Asunto(s)
Senescencia Celular/genética , Células Epiteliales/metabolismo , Genes BRCA1 , Inestabilidad Genómica/genética , Haploinsuficiencia , Glándulas Mamarias Humanas/metabolismo , Acortamiento del Telómero/genética , Daño del ADN , Células Epiteliales/citología , Heterocigoto , Humanos , Glándulas Mamarias Humanas/citología , Mutación , Proteína de Retinoblastoma/genética , Proteína de Retinoblastoma/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
13.
Breast Cancer Res Treat ; 141(2): 231-42, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24036693

RESUMEN

Telomere shortening is a common event involved in malignant transformation. Critically short telomeres may trigger chromosomal aberrations and produce genomic instability leading to cancer development. Therefore, telomere shortening is a frequent molecular alteration in early stages of many epithelial tumors and in breast cancer correlates with stage and prognosis. A better understanding of the involvement of short telomeres in tumors may have a significant impact on patient management and the design of more specific treatments. To understand the role of telomere length (TL) in breast cancer etiology we measured the length of individual telomere signals in single cells by using quantitative telomere in situ hybridization in paraffin-embedded tissue from hereditary and sporadic breast cancers. A total of 104 tumor tissue samples from 75 familial breast tumors (BRCA1, n = 14; BRCA2, n = 13; non-BRCA1/2, n = 48) and 29 sporadic tumors were analyzed. Assessment of telomere signal intensity allowed estimation of the mean TL and related variables, such as percentage of critically short telomeres and percentage of cells with short telomeres. These data were correlated with the immunohistochemical expression of molecular breast cancer markers. Hereditary BRCA1, BRCA2, and non-BRCA1/2 tumors were characterized by shorter TL comparing to sporadic tumors. Considering all tumors, tumor grade was a strong risk factor determining the proportion of short telomeres or short telomere cells. Moreover, some histopathological features appeared to be differentially associated to hereditary or sporadic subgroups. Short telomeres correlated with ER-negative tumors in sporadic cases but not in familial cases, whereas a high level of apoptosis was associated with shorter telomeres in hereditary BRCA1 and BRCA2 tumors. In addition, TL helped to define a subset of non-BRCA1/2 tumors with short telomeres associated with increased expression of antiapoptotic proteins. These findings highlight the potential interest of TL measurements as markers of aggressiveness in breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Acortamiento del Telómero , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Genes BRCA1 , Genes BRCA2 , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mutación , Clasificación del Tumor
14.
PLoS One ; 8(6): e65541, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23762389

RESUMEN

To get further insight into the factors involved in the maintenance of genome integrity we performed a screening of Saccharomyces cerevisiae deletion strains inducing hyperrecombination. We have identified trf4, a gene encoding a non-canonical polyA-polymerase involved in RNA surveillance, as a factor that prevents recombination between DNA repeats. We show that trf4Δ confers a transcription-associated recombination phenotype that is mediated by the nascent mRNA. In addition, trf4Δ also leads to an increase in the mutation frequency. Both genetic instability phenotypes can be suppressed by overexpression of RNase H and are exacerbated by overexpression of the human cytidine deaminase AID. These results suggest that in the absence of Trf4 R-loops accumulate co-transcriptionally increasing the recombination and mutation frequencies. Altogether our data indicate that Trf4 is necessary for both mRNA surveillance and maintenance of genome integrity, serving as a link between RNA and DNA metabolism in S. cerevisiae.


Asunto(s)
ADN Polimerasa Dirigida por ADN/genética , Genoma Fúngico/genética , Mutación/genética , Conformación de Ácido Nucleico , ARN de Hongos/metabolismo , Recombinación Genética , Proteínas de Saccharomyces cerevisiae/genética , Transcripción Genética , Adenosina Desaminasa/metabolismo , Biocatálisis , ADN Polimerasa Dirigida por ADN/química , ADN Polimerasa Dirigida por ADN/metabolismo , Inestabilidad Genómica/genética , Humanos , Fenotipo , Poliadenilación/genética , Estructura Terciaria de Proteína , ARN de Hongos/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
15.
Nat Genet ; 45(5): 526-30, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23502782

RESUMEN

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. We have analyzed exome sequencing data from 127 individuals with CLL and Sanger sequencing data from 214 additional affected individuals, identifying recurrent somatic mutations in POT1 (encoding protection of telomeres 1) in 3.5% of the cases, with the frequency reaching 9% when only individuals without IGHV@ mutations were considered. POT1 encodes a component of the shelterin complex and is the first member of this telomeric structure found to be mutated in human cancer. Somatic mutation of POT1 primarily occurs in gene regions encoding the two oligonucleotide-/oligosaccharide-binding (OB) folds and affects key residues required to bind telomeric DNA. POT1-mutated CLL cells have numerous telomeric and chromosomal abnormalities that suggest that POT1 mutations favor the acquisition of the malignant features of CLL cells. The identification of POT1 as a new frequently mutated gene in CLL may facilitate novel approaches for the clinical management of this disease.


Asunto(s)
Exoma/genética , Leucemia Linfocítica Crónica de Células B/genética , Mutación/genética , Proteínas de Unión a Telómeros/genética , Telómero/genética , Secuencia de Aminoácidos , Aberraciones Cromosómicas , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Datos de Secuencia Molecular , Oligonucleótidos/metabolismo , Oligosacáridos/metabolismo , Unión Proteica , Conformación Proteica , Homología de Secuencia de Aminoácido , Complejo Shelterina , Proteínas de Unión a Telómeros/química , Proteínas de Unión a Telómeros/metabolismo , Células Tumorales Cultivadas
16.
Cell ; 148(6): 1293-307, 2012 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-22424236

RESUMEN

Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity.


Asunto(s)
Genoma Humano , Genómica , Medicina de Precisión , Diabetes Mellitus Tipo 2/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Metabolómica , Persona de Mediana Edad , Mutación , Proteómica , Virus Sincitiales Respiratorios/aislamiento & purificación , Rhinovirus/aislamiento & purificación
17.
Nat Med ; 17(10): 1225-7, 2011 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-21892181

RESUMEN

Here we describe the isolation of stem cells of the human colonic epithelium. Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows the purification of different cell types from human colon mucosa biopsies. The highest EPHB2 surface levels correspond to epithelial colonic cells with the longest telomeres and elevated expression of intestinal stem cell (ISC) marker genes. Moreover, using culturing conditions that recreate the ISC niche, a substantial proportion of EPHB2-high cells can be expanded in vitro as an undifferentiated and multipotent population.


Asunto(s)
Colon/citología , Mucosa Intestinal/citología , Células Madre Multipotentes/fisiología , Receptor EphB2/metabolismo , Diferenciación Celular/fisiología , Proliferación Celular , Citometría de Flujo , Humanos , Inmunohistoquímica , Microscopía Confocal , Células Madre Multipotentes/citología , Reacción en Cadena en Tiempo Real de la Polimerasa , Telómero/metabolismo
18.
Nucleic Acids Res ; 39(14): 6002-15, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21511814

RESUMEN

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron-sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron-sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron-sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.


Asunto(s)
Núcleo Celular/genética , Inestabilidad Genómica , Proteínas Hierro-Azufre/biosíntesis , Proteínas Mitocondriales/fisiología , Proteínas de Saccharomyces cerevisiae/fisiología , Daño del ADN , Replicación del ADN , Eliminación de Gen , Regulación Fúngica de la Expresión Génica , Hierro/metabolismo , Proteínas Mitocondriales/genética , Mutación , Recombinasas/metabolismo , Recombinación Genética , Proteína de Replicación C/metabolismo , Ribosomas/metabolismo , Fase S , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Transcripción Genética
19.
Rev. derecho genoma hum ; (33): 127-167, jul.-dic. 2010.
Artículo en Español | IBECS | ID: ibc-92126

RESUMEN

Los progresivos avances experimentados en nuestra sociedad en los últimos decenios han permitido conocer los datos genéticos de las personas y este hallazgo plantea, junto a innegables beneficios, una gran paradoja, pues la información genética puede ser un elemento de estigmatización social y su uso inadecuado puede suponer una fuente de vulneración de los derechos fundamentales, pues es evidente que existen supuesto en los que el riesgo genético, es decir , la predisposición o susceptibilidad de una persona de padecer determinadas enfermedades, puede ser un elemento discriminatorio, particularmente en la esfera contractual (AU)


The continuous advances in our society in the last decades have allowed us to get to know the personal genetic data. Although this discovery has important benefits, it also causes a great paradox, since the genetic information can be an element of social stigma, and its inappropriate use can damage the fundamental rights. It is obvious that there are cases in which the genetic risk, that is, the predisposition of a person to suffer some illnesses, can be a discriminatory element, specially in the contractual field (AU)


Asunto(s)
Humanos , Predisposición Genética a la Enfermedad , Pruebas Genéticas/ética , Privacidad Genética/ética , Prejuicio , Aseguradoras , Derechos del Paciente
20.
J Plant Physiol ; 167(17): 1432-41, 2010 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-20643493

RESUMEN

This study investigates whether, and how, polyamines (PAs) are involved in mature fruit abscission of olive (Olea europaea L.). Physiological abscission was studied in relation to the activation of the abscission zone (AZ), located between fruit and peduncle, from two olive cultivars where the breakstrength profiles and the scanning electron micrographs illustrated differences in the abscission program, under natural conditions, of mature fruit. The localization and activities of diamine oxidase (DAO), polyamine oxidase (PAO) and PA biosynthetic enzymes, together with PA content were investigated in the fruit AZ during development and abscission. The activities of arginine decarboxylase and S-adenosyl-l-methionine decarboxylase in the fruit AZ were significantly increased and decreased, respectively, by mature fruit abscission, in good agreement with the rise in free putrescine (Put), and content in uncommon PAs there, such as homospermidine and cadaverine, while no significant differences in free spermidine (Spd) and spermine (Spm) contents were detected. By contrast, an abscission-induced decrease was noted in the contents of insoluble conjugated Put, Spd and Spm. The maximum activity of PAO coincided with the maximum content of Spd and Spm, and it was localized mainly in parenchyma cells of pith, while DAO was present mainly in parenchyma cells of pith and cortex as well as at the base of the vascular tissue. These results suggest a clear correlation between the PA distribution and mature fruit abscission. The regulation of PA metabolism is discussed in relation to mature fruit abscission.


Asunto(s)
Frutas/crecimiento & desarrollo , Olea/crecimiento & desarrollo , Olea/metabolismo , Poliaminas/metabolismo , Regulación hacia Arriba , Amina Oxidasa (conteniendo Cobre)/metabolismo , Arginasa/metabolismo , Vías Biosintéticas , Carboxiliasas/metabolismo , Diaminas/metabolismo , Frutas/anatomía & histología , Frutas/citología , Frutas/enzimología , Olea/anatomía & histología , Olea/citología , Ornitina Descarboxilasa/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/metabolismo , Transporte de Proteínas , Solubilidad , Poliamino Oxidasa
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