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  1. AU="Espinosa-Alcantud, Maria"
  2. AU="Glover, Warren W"
  3. AU="Tol, Menno B"
  4. AU="Wang, Xuxia"
  5. AU="Eraslan, Basak"
  6. AU="Johan Auwerx"
  7. AU="Sowrirajan, Bharatwaj"

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  1. Article: SIRT7 and p53 interaction in embryonic development and tumorigenesis.

    Vazquez, Berta N / Fernández-Duran, Irene / Hernandez, Yurdiana / Tarighi, Shahriar / Thackray, Joshua K / Espinosa-Alcantud, Maria / Kumari, Poonam / Ianni, Alessandro / Cesaire, Lionel / Braun, Thomas / Esteller, Manel / Tischfield, Jay / Vaquero, Alejandro / Serrano, Lourdes

    Frontiers in cell and developmental biology

    2024  Volume 11, Page(s) 1281730

    Abstract: p53 is a hallmark tumor suppressor due in part to its role in cell cycle progression, DNA damage repair, and cellular apoptosis; its protein activity interrelates with the Sirtuin family of proteins, major regulators of the cellular response to metabolic, ...

    Abstract p53 is a hallmark tumor suppressor due in part to its role in cell cycle progression, DNA damage repair, and cellular apoptosis; its protein activity interrelates with the Sirtuin family of proteins, major regulators of the cellular response to metabolic, oxidative, and genotoxic stress. In the recent years, mammalian Sirtuin 7 (SIRT7) has emerged as a pivotal regulator of p53, fine-tuning its activity in a context dependent manner. SIRT7 is frequently overexpressed in human cancer, yet its precise role in tumorigenesis and whether it involves p53 regulation is insufficiently understood. Depletion of SIRT7 in mice results in impaired embryo development and premature aging. While p53 activity has been suggested to contribute to tissue specific dysfunction in adult
    Language English
    Publishing date 2024-01-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1281730
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A complex interplay between H2A.Z and HP1 isoforms regulates pericentric heterochromatin.

    González, Jessica / Bosch-Presegué, Laia / Marazuela-Duque, Anna / Guitart-Solanes, Anna / Espinosa-Alcantud, María / Fernandez, Agustín F / Brown, Jeremy P / Ausió, Juan / Vazquez, Berta N / Singh, Prim B / Fraga, Mario F / Vaquero, Alejandro

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1293122

    Abstract: Pericentric heterochromatin (PCH) plays an essential role in the maintenance of genome integrity and alterations in PCH have been linked to cancer and aging. HP1 α, β, and γ, are hallmarks of constitutive heterochromatin that are thought to promote PCH ... ...

    Abstract Pericentric heterochromatin (PCH) plays an essential role in the maintenance of genome integrity and alterations in PCH have been linked to cancer and aging. HP1 α, β, and γ, are hallmarks of constitutive heterochromatin that are thought to promote PCH structure through binding to heterochromatin-specific histone modifications and interaction with a wide range of factors. Among the less understood components of PCH is the histone H2A variant H2A.Z, whose role in the organization and maintenance of PCH is poorly defined. Here we show that there is a complex interplay between H2A.Z and HP1 isoforms in PCH. While the loss of HP1α results in the accumulation of H2A.Z.1 in PCH, which is associated with a significant decrease in its mobile fraction, H2A.Z.1 binds preferentially to HP1β in these regions. Of note, H2A.Z.1 downregulation results in increased heterochromatinization and instability of PCH, reflected by accumulation of the major epigenetic hallmarks of heterochromatin in these regions and increased frequency of chromosome aberrations related to centromeric/pericentromeric defects. Our studies support a role for H2A.Z in genome stability and unveil a key role of H2A.Z in the regulation of heterochromatin-specific epigenetic modifications through a complex interplay with the HP1 isoforms.
    Language English
    Publishing date 2023-11-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1293122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Yeast Biodiversity in Fermented Doughs and Raw Cereal Matrices and the Study of Technological Traits of Selected Strains Isolated in Spain

    Chiva, Rosana / Celador-Lera, Lorena / Uña, José Antonio / Jiménez-López, Ana / Espinosa-Alcantud, María / Mateos-Horganero, Enrique / Vega, Soledad / Santos, María Ángeles / Velázquez, Encarna / Tamame, Mercedes

    Microorganisms. 2020 Dec. 26, v. 9, no. 1

    2020  

    Abstract: Bakers use pure microorganisms and/or traditional sourdoughs as the leavening agent for making bread. The performance of each starter and the substances produced by the microorganisms greatly affect the dough rheology and features of breads. Modern ... ...

    Abstract Bakers use pure microorganisms and/or traditional sourdoughs as the leavening agent for making bread. The performance of each starter and the substances produced by the microorganisms greatly affect the dough rheology and features of breads. Modern sourdoughs inoculated with selected lactic acid bacteria and yeasts are microbiologically stable, safer than traditional sourdoughs, and easy to use. However, the commercial repertoire of baker’s yeasts is still limited. Therefore, there is a demand for new strains of yeast species, capable of conferring distinctive traits to breads made from a variety of agri-food matrices, in the design of innovative starters. In this context, we report the first comprehensive study on yeasts isolated from a wide range of fermented doughs, cereal flours, and grains of Spain. Nine yeast species were identified from 433 isolates, which were distributed among separate clades. Moreover, phenotypic traits of potential technological relevance were identified in selected yeast strains. Mother doughs (MDs) showed the greatest yeast biodiversity, whereas commercial Saccharomyces starters or related and wild strains often dominated the bakery doughs. A metataxonomic analysis of wheat and tritordeum MDs revealed a greater richness of yeast species and percentage variations related to the consistency, flour type, and fermentation time of MDs.
    Keywords Saccharomyces ; biodiversity ; design ; fermentation ; flour ; lactic acid bacteria ; phenotype ; rheology ; sourdough ; strains ; wheat ; yeasts ; Spain
    Language English
    Dates of publication 2020-1226
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-light
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9010047
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons.

    Romeo-Guitart, David / Leiva-Rodríguez, Tatiana / Espinosa-Alcantud, María / Sima, Núria / Vaquero, Alejandro / Domínguez-Martín, Helena / Ruano, Diego / Casas, Caty

    Cell death & disease

    2018  Volume 9, Issue 5, Page(s) 531

    Abstract: Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to ...

    Abstract Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.
    MeSH term(s) Acamprosate/pharmacology ; Animals ; Benzamides/pharmacology ; Drug Combinations ; Endoplasmic Reticulum Stress/drug effects ; Endoplasmic Reticulum Stress/genetics ; Enzyme Activation/drug effects ; Enzyme Activation/genetics ; Female ; Hypoglossal Nerve Injuries/drug therapy ; Hypoglossal Nerve Injuries/enzymology ; Hypoglossal Nerve Injuries/genetics ; Hypoglossal Nerve Injuries/pathology ; Mice ; Mice, Knockout ; Motor Neurons/enzymology ; Motor Neurons/pathology ; Neuroprotection/drug effects ; Neuroprotection/genetics ; Ribavirin/pharmacology ; Sirtuin 1/antagonists & inhibitors ; Sirtuin 1/genetics ; Sirtuin 1/metabolism ; Sirtuin 2/antagonists & inhibitors ; Sirtuin 2/genetics ; Sirtuin 2/metabolism ; Sulfonamides/pharmacology
    Chemical Substances 3-(1-azepanylsulfonyl)-N-(3-bromphenyl)benzamide ; Benzamides ; Drug Combinations ; Sulfonamides ; acamprosate, ribavirin drug combination ; Ribavirin (49717AWG6K) ; Sirt1 protein, mouse (EC 3.5.1.-) ; Sirt2 protein, mouse (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-) ; Sirtuin 2 (EC 3.5.1.-) ; Acamprosate (N4K14YGM3J)
    Language English
    Publishing date 2018-05-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-018-0553-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Yeast Biodiversity in Fermented Doughs and Raw Cereal Matrices and the Study of Technological Traits of Selected Strains Isolated in Spain.

    Chiva, Rosana / Celador-Lera, Lorena / Uña, José Antonio / Jiménez-López, Ana / Espinosa-Alcantud, María / Mateos-Horganero, Enrique / Vega, Soledad / Santos, María Ángeles / Velázquez, Encarna / Tamame, Mercedes

    Microorganisms

    2020  Volume 9, Issue 1

    Abstract: Bakers use pure microorganisms and/or traditional sourdoughs as the leavening agent for making bread. The performance of each starter and the substances produced by the microorganisms greatly affect the dough rheology and features of breads. Modern ... ...

    Abstract Bakers use pure microorganisms and/or traditional sourdoughs as the leavening agent for making bread. The performance of each starter and the substances produced by the microorganisms greatly affect the dough rheology and features of breads. Modern sourdoughs inoculated with selected lactic acid bacteria and yeasts are microbiologically stable, safer than traditional sourdoughs, and easy to use. However, the commercial repertoire of baker's yeasts is still limited. Therefore, there is a demand for new strains of yeast species, capable of conferring distinctive traits to breads made from a variety of agri-food matrices, in the design of innovative starters. In this context, we report the first comprehensive study on yeasts isolated from a wide range of fermented doughs, cereal flours, and grains of Spain. Nine yeast species were identified from 433 isolates, which were distributed among separate clades. Moreover, phenotypic traits of potential technological relevance were identified in selected yeast strains. Mother doughs (MDs) showed the greatest yeast biodiversity, whereas commercial
    Language English
    Publishing date 2020-12-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9010047
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: SIRT1 regulates DNA damage signaling through the PP4 phosphatase complex.

    Rasti, George / Becker, Maximilian / Vazquez, Berta N / Espinosa-Alcantud, Maria / Fernández-Duran, Irene / Gámez-García, Andrés / Ianni, Alessandro / Gonzalez, Jessica / Bosch-Presegué, Laia / Marazuela-Duque, Anna / Guitart-Solanes, Anna / Segura-Bayona, Sandra / Bech-Serra, Joan-Josep / Scher, Michael / Serrano, Lourdes / Shankavaram, Uma / Erdjument-Bromage, Hediye / Tempst, Paul / Reinberg, Danny /
    Olivella, Mireia / Stracker, Travis H / de la Torre, Carolina / Vaquero, Alejandro

    Nucleic acids research

    2023  Volume 51, Issue 13, Page(s) 6754–6769

    Abstract: The Sirtuin family of NAD+-dependent enzymes plays an important role in maintaining genome stability upon stress. Several mammalian Sirtuins have been linked directly or indirectly to the regulation of DNA damage during replication through Homologous ... ...

    Abstract The Sirtuin family of NAD+-dependent enzymes plays an important role in maintaining genome stability upon stress. Several mammalian Sirtuins have been linked directly or indirectly to the regulation of DNA damage during replication through Homologous recombination (HR). The role of one of them, SIRT1, is intriguing as it seems to have a general regulatory role in the DNA damage response (DDR) that has not yet been addressed. SIRT1-deficient cells show impaired DDR reflected in a decrease in repair capacity, increased genome instability and decreased levels of γH2AX. Here we unveil a close functional antagonism between SIRT1 and the PP4 phosphatase multiprotein complex in the regulation of the DDR. Upon DNA damage, SIRT1 interacts specifically with the catalytical subunit PP4c and promotes its inhibition by deacetylating the WH1 domain of the regulatory subunits PP4R3α/β. This in turn regulates γH2AX and RPA2 phosphorylation, two key events in the signaling of DNA damage and repair by HR. We propose a mechanism whereby during stress, SIRT1 signaling ensures a global control of DNA damage signaling through PP4.
    MeSH term(s) Animals ; Humans ; DNA Damage ; Mammals/metabolism ; Phosphoric Monoester Hydrolases ; Phosphorylation ; Signal Transduction ; Sirtuin 1/metabolism
    Chemical Substances Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; Sirtuin 1 (EC 3.5.1.-) ; protein phosphatase 4 (EC 3.1.3.16)
    Language English
    Publishing date 2023-06-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1.

    Simonet, Nicolás G / Thackray, Joshua K / Vazquez, Berta N / Ianni, Alessandro / Espinosa-Alcantud, Maria / Morales-Sanfrutos, Julia / Hurtado-Bagès, Sarah / Sabidó, Eduard / Buschbeck, Marcus / Tischfield, Jay / De La Torre, Carolina / Esteller, Manel / Braun, Thomas / Olivella, Mireia / Serrano, Lourdes / Vaquero, Alejandro

    Science advances

    2020  Volume 6, Issue 30, Page(s) eaaz2590

    Abstract: Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5'-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a ... ...

    Abstract Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5'-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, as it also features auto-mADPRT activity. SirT7 mADPRT occurs at a previously undefined active site, and its abrogation alters SirT7 chromatin distribution. We identify an epigenetic pathway by which ADP-ribosyl-SirT7 is recognized by the ADP-ribose reader mH2A1.1 under glucose starvation, inducing SirT7 relocalization to intergenic regions. SirT7 promotes mH2A1 enrichment in a subset of nearby genes, many of them involved in second messenger signaling, resulting in their specific up- or down-regulation. The expression profile of these genes under calorie restriction is consistently abrogated in SirT7-deficient mice, resulting in impaired activation of autophagy. Our work provides a novel perspective on sirtuin duality and suggests a role for SirT7/mH2A1.1 axis in glucose homeostasis and aging.
    Language English
    Publishing date 2020-07-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.aaz2590
    Database MEDical Literature Analysis and Retrieval System OnLINE

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