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  1. AU="Premkumar, Tolkappiyan"
  2. TI=Glycemic Control Improvement in Italian Children and Adolescents With Type 1 Diabetes Followed Through Telemedicine During Lockdown Due to the COVID 19 Pandemic

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  1. Artikel ; Online: Genetic dissection of crossover mutants defines discrete intermediates in mouse meiosis.

    Premkumar, Tolkappiyan / Paniker, Lakshmi / Kang, Rhea / Biot, Mathilde / Humphrey, Ericka / Destain, Honorine / Ferranti, Isabella / Okulate, Iyinyeoluwa / Nguyen, Holly / Kilaru, Vindhya / Frasca, Melissa / Chakraborty, Parijat / Cole, Francesca

    Molecular cell

    2023  Band 83, Heft 16, Seite(n) 2941–2958.e7

    Abstract: Crossovers (COs), the exchange of homolog arms, are required for accurate chromosome segregation during meiosis. Studies in yeast have described the single-end invasion (SEI) intermediate: a stabilized 3' end annealed with the homolog as the first ... ...

    Abstract Crossovers (COs), the exchange of homolog arms, are required for accurate chromosome segregation during meiosis. Studies in yeast have described the single-end invasion (SEI) intermediate: a stabilized 3' end annealed with the homolog as the first detectible CO precursor. SEIs are thought to differentiate into double Holliday junctions (dHJs) that are resolved by MutLgamma (MLH1/MLH3) into COs. Currently, we lack knowledge of early steps of mammalian CO recombination or how intermediates are differentiated in any organism. Using comprehensive analysis of recombination in thirteen different genetic conditions with varying levels of compromised CO resolution, we infer CO precursors include asymmetric SEI-like intermediates and dHJs in mouse. In contrast to yeast, MLH3 is structurally required to differentiate CO precursors into dHJs. We verify conservation of aspects of meiotic recombination and show unique features in mouse, providing mechanistic insight into CO formation.
    Mesh-Begriff(e) Animals ; Mice ; Saccharomyces cerevisiae/genetics ; Meiosis/genetics ; Chromosome Segregation/genetics ; DNA, Cruciform/genetics ; Mammals
    Chemische Substanzen DNA, Cruciform
    Sprache Englisch
    Erscheinungsdatum 2023-08-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2023.07.022
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Meiotic DNA break repair can utilize homolog-independent chromatid templates in C. elegans.

    Toraason, Erik / Horacek, Anna / Clark, Cordell / Glover, Marissa L / Adler, Victoria L / Premkumar, Tolkappiyan / Salagean, Alina / Cole, Francesca / Libuda, Diana E

    Current biology : CB

    2021  Band 31, Heft 7, Seite(n) 1508–1514.e5

    Abstract: During meiosis, the maintenance of genome integrity is critical for generating viable haploid gametes. ...

    Abstract During meiosis, the maintenance of genome integrity is critical for generating viable haploid gametes.
    Mesh-Begriff(e) Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins ; Chromatids/genetics ; DNA Breaks, Double-Stranded ; DNA Helicases ; DNA Repair ; Meiosis/genetics
    Chemische Substanzen Caenorhabditis elegans Proteins ; XPF-1 protein, C elegans (EC 3.1.-) ; DNA Helicases (EC 3.6.4.-)
    Sprache Englisch
    Erscheinungsdatum 2021-03-18
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2021.03.008
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: A transcriptional coregulator, SPIN·DOC, attenuates the coactivator activity of Spindlin1.

    Bae, Narkhyun / Gao, Min / Li, Xu / Premkumar, Tolkappiyan / Sbardella, Gianluca / Chen, Junjie / Bedford, Mark T

    The Journal of biological chemistry

    2017  Band 292, Heft 51, Seite(n) 20808–20817

    Abstract: Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. SPIN1 harbors three Tudor domains, two of which engage the tail of histone H3 by reading the H3-Lys-4 trimethylation and H3- ... ...

    Abstract Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. SPIN1 harbors three Tudor domains, two of which engage the tail of histone H3 by reading the H3-Lys-4 trimethylation and H3-Arg-8 asymmetric dimethylation marks. To gain mechanistic insight into how SPIN1 functions as a transcriptional coactivator, here we purified its interacting proteins. We identified an uncharacterized protein (C11orf84), which we renamed SPIN1 docking protein (SPIN·DOC), that directly binds SPIN1 and strongly disrupts its histone methylation reading ability, causing it to disassociate from chromatin. The Spindlin family of coactivators has five related members (SPIN1, 2A, 2B, 3, and 4), and we found that all of them bind SPIN·DOC. It has been reported previously that SPIN1 regulates gene expression in the Wnt signaling pathway by directly interacting with transcription factor 4 (TCF4). We observed here that SPIN·DOC associates with TCF4 in a SPIN1-dependent manner and dampens SPIN1 coactivator activity in TOPflash reporter assays. Furthermore, knockdown and overexpression experiments indicated that SPIN·DOC represses the expression of a number of SPIN1-regulated genes, including those encoding ribosomal RNA and the cytokine IL1B. In conclusion, we have identified SPIN·DOC as a transcriptional repressor that binds SPIN1 and masks its ability to engage the H3-Lys-4 trimethylation activation mark.
    Mesh-Begriff(e) Carrier Proteins/chemistry ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chromatin/metabolism ; Co-Repressor Proteins/chemistry ; Co-Repressor Proteins/genetics ; Co-Repressor Proteins/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; HEK293 Cells ; Histones/metabolism ; Humans ; Methylation ; Microtubule-Associated Proteins/chemistry ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Interaction Domains and Motifs ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Trans-Activators/chemistry ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factor 4/metabolism ; Wnt Signaling Pathway
    Chemische Substanzen Carrier Proteins ; Cell Cycle Proteins ; Chromatin ; Co-Repressor Proteins ; Histones ; Microtubule-Associated Proteins ; Phosphoproteins ; Recombinant Fusion Proteins ; SPINDOC protein, human ; TCF4 protein, human ; Trans-Activators ; Transcription Factor 4 ; spindlin
    Sprache Englisch
    Erscheinungsdatum 2017-10-23
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M117.814913
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: RB localizes to DNA double-strand breaks and promotes DNA end resection and homologous recombination through the recruitment of BRG1.

    Vélez-Cruz, Renier / Manickavinayaham, Swarnalatha / Biswas, Anup K / Clary, Regina Weaks / Premkumar, Tolkappiyan / Cole, Francesca / Johnson, David G

    Genes & development

    2016  Band 30, Heft 22, Seite(n) 2500–2512

    Abstract: The retinoblastoma (RB) tumor suppressor is recognized as a master regulator that controls entry into the S phase of the cell cycle. Its loss leads to uncontrolled cell proliferation and is a hallmark of cancer. RB works by binding to members of the E2F ... ...

    Abstract The retinoblastoma (RB) tumor suppressor is recognized as a master regulator that controls entry into the S phase of the cell cycle. Its loss leads to uncontrolled cell proliferation and is a hallmark of cancer. RB works by binding to members of the E2F family of transcription factors and recruiting chromatin modifiers to the promoters of E2F target genes. Here we show that RB also localizes to DNA double-strand breaks (DSBs) dependent on E2F1 and ATM kinase activity and promotes DSB repair through homologous recombination (HR), and its loss results in genome instability. RB is necessary for the recruitment of the BRG1 ATPase to DSBs, which stimulates DNA end resection and HR. A knock-in mutation of the ATM phosphorylation site on E2F1 (S29A) prevents the interaction between E2F1 and TopBP1 and recruitment of RB, E2F1, and BRG1 to DSBs. This knock-in mutation also impairs DNA repair, increases genomic instability, and renders mice hypersensitive to IR. Importantly, depletion of RB in osteosarcoma and breast cancer cell lines results in sensitivity to DNA-damaging drugs, which is further exacerbated by poly-ADP ribose polymerase (PARP) inhibitors. We uncovered a novel, nontranscriptional function for RB in HR, which could contribute to genome instability associated with RB loss.
    Mesh-Begriff(e) Animals ; Cell Line ; Cell Line, Tumor ; DNA Breaks, Double-Stranded/drug effects ; DNA Breaks, Double-Stranded/radiation effects ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA Repair/genetics ; E2F1 Transcription Factor/genetics ; E2F1 Transcription Factor/metabolism ; Gamma Rays ; Gene Knock-In Techniques ; Genomic Instability/genetics ; Homologous Recombination/genetics ; Humans ; Male ; Mice ; Mutagens/pharmacology ; Mutation ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Protein Transport/genetics ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Whole-Body Irradiation/mortality
    Chemische Substanzen E2F1 Transcription Factor ; E2f1 protein, mouse ; Mutagens ; Nuclear Proteins ; Poly(ADP-ribose) Polymerase Inhibitors ; Retinoblastoma Protein ; Transcription Factors ; Smarca4 protein, mouse (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
    Sprache Englisch
    Erscheinungsdatum 2016-11-15
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 806684-x
    ISSN 1549-5477 ; 0890-9369
    ISSN (online) 1549-5477
    ISSN 0890-9369
    DOI 10.1101/gad.288282.116
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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