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  1. Article: Letter from A. J. Miller, M. D.

    Miller, A J

    The Chicago medical journal

    2023  Volume 25, Issue 16, Page(s) 532–537

    Language English
    Publishing date 2023-07-06
    Publishing country United States
    Document type Journal Article
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Bernard J. Miller, M.D., Sc.D. (Hon.) (1918-2007): The Life and Scientific Contributions of a Crucial Figure in the Development of the Heart-Lung Machine.

    Bauer, Tyler M / Dworkin, Myles S / Miller, Stanton B / Yeo, Charles J / Cowan, Scott W

    The American surgeon

    2019  Volume 84, Issue 11, Page(s) e472–e474

    MeSH term(s) Heart-Lung Machine/history ; History, 20th Century ; Humans ; United States
    Language English
    Publishing date 2019-02-12
    Publishing country United States
    Document type Biography ; Historical Article ; Journal Article ; Portrait
    ZDB-ID 202465-2
    ISSN 1555-9823 ; 0003-1348
    ISSN (online) 1555-9823
    ISSN 0003-1348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Baseline identification of clonal V(D)J sequences for DNA-based minimal residual disease detection in multiple myeloma.

    Rustad, Even H / Hultcrantz, Malin / Yellapantula, Venkata D / Akhlaghi, Theresia / Ho, Caleb / Arcila, Maria E / Roshal, Mikhail / Patel, Akshar / Chen, Denise / Devlin, Sean M / Jacobsen, Austin / Huang, Ying / Miller, Jeffrey E / Papaemmanuil, Elli / Landgren, Ola

    PloS one

    2019  Volume 14, Issue 3, Page(s) e0211600

    Abstract: Tracking of clonal immunoglobulin V(D)J rearrangement sequences by next generation sequencing is ... variable rates of V(D)J sequence identification at baseline, which could limit tracking. Here, we aimed ... to define the factors influencing the identification of clonal V(D)J sequences. Bone marrow mononuclear ...

    Abstract Tracking of clonal immunoglobulin V(D)J rearrangement sequences by next generation sequencing is highly sensitive for minimal residual disease in multiple myeloma. However, previous studies have found variable rates of V(D)J sequence identification at baseline, which could limit tracking. Here, we aimed to define the factors influencing the identification of clonal V(D)J sequences. Bone marrow mononuclear cells from 177 myeloma patients underwent V(D)J sequencing by the LymphoTrack assays (Invivoscribe). As a molecular control for tumor cell content, we sequenced the samples using our in-house myeloma panel myTYPE. V(D)J sequence clonality was identified in 81% of samples overall, as compared with 95% in samples where tumor-derived DNA was detectable by myTYPE. Clonality was detected more frequently in patients with lambda-restricted disease, mainly because of increased detection of kappa gene rearrangements. Finally, we describe how the tumor cell content of bone marrow aspirates decrease gradually in sequential pulls because of hemodilution: From the initial pull used for aspirate smear, to the final pull that is commonly used for research. In conclusion, baseline clonality detection rates of 95% or higher are feasible in multiple myeloma. Optimal performance depends on the use of good quality aspirates and/or subsequent tumor cell enrichment.
    MeSH term(s) Aged ; Bone Marrow Cells/metabolism ; Female ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin kappa-Chains/genetics ; Male ; Middle Aged ; Multiple Myeloma/diagnosis ; Multiple Myeloma/genetics ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/genetics ; Sequence Analysis, DNA ; V(D)J Recombination
    Chemical Substances Immunoglobulin Heavy Chains ; Immunoglobulin kappa-Chains
    Language English
    Publishing date 2019-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0211600
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Baseline identification of clonal V(D)J sequences for DNA-based minimal residual disease detection in multiple myeloma.

    Even H Rustad / Malin Hultcrantz / Venkata D Yellapantula / Theresia Akhlaghi / Caleb Ho / Maria E Arcila / Mikhail Roshal / Akshar Patel / Denise Chen / Sean M Devlin / Austin Jacobsen / Ying Huang / Jeffrey E Miller / Elli Papaemmanuil / Ola Landgren

    PLoS ONE, Vol 14, Iss 3, p e

    2019  Volume 0211600

    Abstract: Tracking of clonal immunoglobulin V(D)J rearrangement sequences by next generation sequencing is ... variable rates of V(D)J sequence identification at baseline, which could limit tracking. Here, we aimed ... to define the factors influencing the identification of clonal V(D)J sequences. Bone marrow mononuclear ...

    Abstract Tracking of clonal immunoglobulin V(D)J rearrangement sequences by next generation sequencing is highly sensitive for minimal residual disease in multiple myeloma. However, previous studies have found variable rates of V(D)J sequence identification at baseline, which could limit tracking. Here, we aimed to define the factors influencing the identification of clonal V(D)J sequences. Bone marrow mononuclear cells from 177 myeloma patients underwent V(D)J sequencing by the LymphoTrack assays (Invivoscribe). As a molecular control for tumor cell content, we sequenced the samples using our in-house myeloma panel myTYPE. V(D)J sequence clonality was identified in 81% of samples overall, as compared with 95% in samples where tumor-derived DNA was detectable by myTYPE. Clonality was detected more frequently in patients with lambda-restricted disease, mainly because of increased detection of kappa gene rearrangements. Finally, we describe how the tumor cell content of bone marrow aspirates decrease gradually in sequential pulls because of hemodilution: From the initial pull used for aspirate smear, to the final pull that is commonly used for research. In conclusion, baseline clonality detection rates of 95% or higher are feasible in multiple myeloma. Optimal performance depends on the use of good quality aspirates and/or subsequent tumor cell enrichment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: J/psi production and nuclear effects for d + Au and p + p collisions at square root of S(NN) = 200 GeV.

    Adler, S S / Afanasiev, S / Aidala, C / Ajitanand, N N / Akiba, Y / Al-Jamel, A / Alexander, J / Aoki, K / Aphecetche, L / Armendariz, R / Aronson, S H / Atomssa, E T / Averbeck, R / Awes, T C / Babintsev, V / Baldisseri, A / Barish, K N / Barnes, P D / Bassalleck, B /
    Bathe, S / Batsouli, S / Baublis, V / Bauer, F / Bazilevsky, A / Belikov, S / Bjorndal, M T / Boissevain, J G / Borel, H / Brooks, M L / Brown, D S / Bruner, N / Bucher, D / Buesching, H / Bumazhnov, V / Bunce, G / Burward-Hoy, J M / Butsyk, S / Camard, X / Chand, P / Chang, W C / Chernichenko, S / Chi, C Y / Chiba, J / Chiu, M / Choi, I J / Choudhury, R K / Chujo, T / Cianciolo, V / Cobigo, Y / Cole, B A / Comets, M P / Constantin, P / Csanád, M / Csörgo, T / Cussonneau, J P / d'Enterria, D / Das, K / David, G / Deák, F / Delagrange, H / Denisov, A / Deshpande, A / Desmond, E J / Devismes, A / Dietzsch, O / Drachenberg, J L / Drapier, O / Drees, A / Durum, A / Dutta, D / Dzhordzhadze, V / Efremenko, Y V / En'yo, H / Espagnon, B / Esumi, S / Fields, D E / Finck, C / Fleuret, F / Fokin, S L / Fox, B D / Fraenkel, Z / Frantz, J E / Franz, A / Frawley, A D / Fukao, Y / Fung, S-Y / Gadrat, S / Germain, M / Glenn, A / Gonin, M / Gosset, J / Goto, Y / Granier de Cassagnac, R / Grau, N / Greene, S V / Grosse Perdekamp, M / Gustafsson, H-A / Hachiya, T / Haggerty, J S / Hamagaki, H / Hansen, A G / Hartouni, E P / Harvey, M / Hasuko, K / Hayano, R / He, X / Heffner, M / Hemmick, T K / Heuser, J M / Hidas, P / Hiejima, H / Hill, J C / Hobbs, R / Holzmann, W / Homma, K / Hong, B / Hoover, A / Horaguchi, T / Ichihara, T / Ikonnikov, V V / Imai, K / Inaba, M / Inuzuka, M / Isenhower, D / Isenhower, L / Ishihara, M / Issah, M / Isupov, A / Jacak, B V / Jia, J / Jinnouchi, O / Johnson, B M / Johnson, S C / Joo, K S / Jouan, D / Kajihara, F / Kametani, S / Kamihara, N / Kaneta, M / Kang, J H / Katou, K / Kawabata, T / Kazantsev, A V / Kelly, S / Khachaturov, B / Khanzadeev, A / Kikuchi, J / Kim, D J / Kim, E / Kim, G-B / Kim, H J / Kinney, E / Kiss, A / Kistenev, E / Kiyomichi, A / Klein-Boesing, C / Kobayashi, H / Kochenda, L / Kochetkov, V / Kohara, R / Komkov, B / Konno, M / Kotchetkov, D / Kozlov, A / Kroon, P J / Kuberg, C H / Kunde, G J / Kurita, K / Kweon, M J / Kwon, Y / Kyle, G S / Lacey, R / Lajoie, J G / Le Bornec, Y / Lebedev, A / Leckey, S / Lee, D M / Leitch, M J / Leite, M A L / Li, X H / Lim, H / Litvinenko, A / Liu, M X / Maguire, C F / Makdisi, Y I / Malakhov, A / Manko, V I / Mao, Y / Martinez, G / Masui, H / Matathias, F / Matsumoto, T / McCain, M C / McGaughey, P L / Miake, Y / Miller, T E / Milov, A / Mioduszewski, S / Mishra, G C / Mitchell, J T / Mohanty, A K / Morrison, D P / Moss, J M / Mukhopadhyay, D / Muniruzzaman, M / Nagamiya, S / Nagle, J L / Nakamura, T / Newby, J / Nyanin, A S / Nystrand, J / O'brien, E / Ogilvie, C A / Ohnishi, H / Ojha, I D / Okada, H / Okada, K / Oskarsson, A / Otterlund, I / Oyama, K / Ozawa, K / Pal, D / Palounek, A P T / Pantuev, V / Papavassiliou, V / Park, J / Park, W J / Pate, S F / Pei, H / Penev, V / Peng, J-C / Pereira, H / Peresedov, V / Pierson, A / Pinkenburg, C / Pisani, R P / Purschke, M L / Purwar, A K / Qualls, J M / Rak, J / Ravinovich, I / Read, K F / Reuter, M / Reygers, K / Riabov, V / Riabov, Y / Roche, G / Romana, A / Rosati, M / Rosendahl, S S E / Rosnet, P / Rykov, V L / Ryu, S S / Saito, N / Sakaguchi, T / Sakai, S / Samsonov, V / Sanfratello, L / Santo, R / Sato, H D / Sato, S / Sawada, S / Schutz, Y / Semenov, V / Seto, R / Shea, T K / Shein, I / Shibata, T-A / Shigaki, K / Shimomura, M / Sickles, A / Silva, C L / Silvermyr, D / Sim, K S / Soldatov, A / Soltz, R A / Sondheim, W E / Sorensen, S P / Sourikova, I V / Staley, F / Stankus, P W / Stenlund, E / Stepanov, M / Ster, A / Stoll, S P / Sugitate, T / Sullivan, J P / Takagi, S / Takagui, E M / Taketani, A / Tanaka, K H / Tanaka, Y / Tanida, K / Tannenbaum, M J / Taranenko, A / Tarján, P / Thomas, T L / Togawa, M / Tojo, J / Torii, H / Towell, R S / Tram, V-N / Tserruya, I / Tsuchimoto, Y / Tydesjö, H / Tyurin, N / Uam, T J / van Hecke, H W / Velkovska, J / Velkovsky, M / Veszprémi, V / Vinogradov, A A / Volkov, M A / Vznuzdaev, E / Wang, X R / Watanabe, Y / White, S N / Willis, N / Wohn, F K / Woody, C L / Xie, W / Yanovich, A / Yokkaichi, S / Young, G R / Yushmanov, I E / Zajc, W A / Zhang, C / Zhou, S / Zimányi, J / Zolin, L / Zong, X

    Physical review letters

    2006  Volume 96, Issue 1, Page(s) 12304

    Abstract: J/psi production in d + Au and p + p collisions at square root of S(NN) = 200 GeV has been measured ... by the PHENIX experiment at rapidities -2.2 < y < +2.4. The cross sections and nuclear dependence of J/psi ... A results and to theoretical models. The observed nuclear dependence in d + Au collisions is found to be ...

    Abstract J/psi production in d + Au and p + p collisions at square root of S(NN) = 200 GeV has been measured by the PHENIX experiment at rapidities -2.2 < y < +2.4. The cross sections and nuclear dependence of J/psi production versus rapidity, transverse momentum, and centrality are obtained and compared to lower energy p + A results and to theoretical models. The observed nuclear dependence in d + Au collisions is found to be modest, suggesting that the absorption in the final state is weak and the shadowing of the gluon distributions is small and consistent with Dokshitzer-Gribov-Lipatov-Altarelli-Parisi-based parametrizations that fit deep-inelastic scattering and Drell-Yan data at lower energies.
    Language English
    Publishing date 2006-01-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.96.012304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination.

    Lee, Baeck-Seung / Gapud, Eric J / Zhang, Shichuan / Dorsett, Yair / Bredemeyer, Andrea / George, Rosmy / Callen, Elsa / Daniel, Jeremy A / Osipovich, Oleg / Oltz, Eugene M / Bassing, Craig H / Nussenzweig, Andre / Lees-Miller, Susan / Hammel, Michal / Chen, Benjamin P C / Sleckman, Barry P

    Molecular and cellular biology

    2013  Volume 33, Issue 18, Page(s) 3568–3579

    Abstract: V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks ... serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs ...

    Abstract V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs have unique functions in the repair of coding DNA ends. ATM deficiency leads to instability of postcleavage complexes and the loss of coding ends from these complexes. DNA-PKcs deficiency leads to a nearly complete block in coding join formation, as DNA-PKcs is required to activate Artemis, the endonuclease that opens hairpin-sealed coding ends. In contrast to loss of DNA-PKcs protein, here we show that inhibition of DNA-PKcs kinase activity has no effect on coding join formation when ATM is present and its kinase activity is intact. The ability of ATM to compensate for DNA-PKcs kinase activity depends on the integrity of three threonines in DNA-PKcs that are phosphorylation targets of ATM, suggesting that ATM can modulate DNA-PKcs activity through direct phosphorylation of DNA-PKcs. Mutation of these threonine residues to alanine (DNA-PKcs(3A)) renders DNA-PKcs dependent on its intrinsic kinase activity during coding end joining, at a step downstream of opening hairpin-sealed coding ends. Thus, DNA-PKcs has critical functions in coding end joining beyond promoting Artemis endonuclease activity, and these functions can be regulated redundantly by the kinase activity of either ATM or DNA-PKcs.
    MeSH term(s) Animals ; Ataxia Telangiectasia Mutated Proteins/chemistry ; Ataxia Telangiectasia Mutated Proteins/genetics ; Ataxia Telangiectasia Mutated Proteins/metabolism ; Catalytic Domain ; Cells, Cultured ; DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA-Activated Protein Kinase/chemistry ; DNA-Activated Protein Kinase/genetics ; DNA-Activated Protein Kinase/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Endonucleases/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Mice ; Nuclear Proteins/chemistry ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Phosphorylation ; Precursor Cells, B-Lymphoid/metabolism ; Protein Interaction Domains and Motifs ; V(D)J Recombination
    Chemical Substances DNA-Binding Proteins ; Homeodomain Proteins ; Nuclear Proteins ; Rag2 protein, mouse ; RAG-1 protein (128559-51-3) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Atm protein, mouse (EC 2.7.11.1) ; DNA-Activated Protein Kinase (EC 2.7.11.1) ; Prkdc protein, mouse (EC 2.7.11.1) ; Endonucleases (EC 3.1.-) ; Dclre1c protein, mouse (EC 3.1.-.-)
    Language English
    Publishing date 2013-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00308-13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Re: Application of artificial intelligence to the management of urological cancer. M. F. Abbod, J. W. Catto, D. A. Linkens and F. C. Hamdy J Urol 2007; 178: 1150-1156.

    Stephan, Carsten / Cammann, Henning / Lein, Michael / Miller, Kurt / Jung, Klaus

    The Journal of urology

    2008  Volume 179, Issue 5, Page(s) 2067

    MeSH term(s) Artificial Intelligence ; Humans ; Male ; Prostatic Neoplasms/diagnosis
    Language English
    Publishing date 2008-05
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 3176-8
    ISSN 1527-3792 ; 0022-5347
    ISSN (online) 1527-3792
    ISSN 0022-5347
    DOI 10.1016/j.juro.2008.01.053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Online: Investigation of cell fate decision in Schizosaccharomyces pombe by ncRNA annotation and statistical analyses, supplementary data to: Bitton, Danny A; Grallert, Agnes; Scutt, Paul J; Yates, Tim; Yaoyong, Li; Bradford, James R; Hey, Yvonne; Pepper, Stuart D; Hagan, Iain M; Miller, Crispin J (2011): Programmed fluctuations in sense/antisense transcript ratios drive sexual differentiation in S. pombe. Molecular Systems Biology, 7

    Bitton, Danny A / Bradford, James R / Grallert, Agnes / Hagan, Iain M / Hey, Yvonne / Miller, Crispin J / Pepper, Stuart D / Scutt, Paul J / Yaoyong, Li / Yates, Tim

    2012  

    Abstract: Studies in the fission yeast Schizosaccharomyces pombe (S. pombe) have done much to inform the view of heterochromatin and its control by the RNA interference (RNAi) machinery. Using cDNA synthesised from poly(A)-enriched RNA samples, numerous novel ... ...

    Abstract Studies in the fission yeast Schizosaccharomyces pombe (S. pombe) have done much to inform the view of heterochromatin and its control by the RNA interference (RNAi) machinery. Using cDNA synthesised from poly(A)-enriched RNA samples, numerous novel ncRNA loci were discovered, and the 50 and 30 ends of many other genes were refined in previous studies. Although some of these transcripts may encode novel proteins the function of the majority is yet to be determined. The authors have used strand-specific deep sequencing of RNA, irrespective of poly(A) status, to reveal a highly structured antisense programme that modulates gene expression to dictate cell fate decisions during sexual differentiation. They show that an extensive and elaborate array of ncRNA production accompanies sexual differentiation in the fission yeast S. pombe. Experimental manipulation suggests that these transcripts specifically regulate the function of the target genes.
    Language English
    Dates of publication 2012-9999
    Size Online-Ressource
    Publisher PANGAEA - Data Publisher for Earth & Environmental Science
    Publishing place Bremen/Bremerhaven
    Document type Book ; Online
    Note This dataset is supplement to doi:10.1038/msb.2011.90
    DOI 10.1594/PANGAEA.775713
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  9. Article ; Online: Functional Intersection of ATM and DNA-Dependent Protein Kinase Catalytic Subunit in Coding End Joining during V(D)J Recombination

    Lee, Baeck-Seung / Gapud, Eric J. / Zhang, Shichuan / Dorsett, Yair / Bredemeyer, Andrea / George, Rosmy / Callen, Elsa / Daniel, Jeremy A. / Osipovich, Oleg / Oltz, Eugene M. / Bassing, Craig H. / Nussenzweig, Andre / Lees-Miller, Susan / Hammel, Michal / Chen, Benjamin P. C. / Sleckman, Barry P.

    Molecular and Cellular Biology. 2013 Sept. 1, v. 33, no. 18 p.3568-3579

    2013  

    Abstract: V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks ... serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs ...

    Abstract V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs have unique functions in the repair of coding DNA ends. ATM deficiency leads to instability of postcleavage complexes and the loss of coding ends from these complexes. DNA-PKcs deficiency leads to a nearly complete block in coding join formation, as DNA-PKcs is required to activate Artemis, the endonuclease that opens hairpin-sealed coding ends. In contrast to loss of DNA-PKcs protein, here we show that inhibition of DNA-PKcs kinase activity has no effect on coding join formation when ATM is present and its kinase activity is intact. The ability of ATM to compensate for DNA-PKcs kinase activity depends on the integrity of three threonines in DNA-PKcs that are phosphorylation targets of ATM, suggesting that ATM can modulate DNA-PKcs activity through direct phosphorylation of DNA-PKcs. Mutation of these threonine residues to alanine (DNA-PKcs³ᴬ) renders DNA-PKcs dependent on its intrinsic kinase activity during coding end joining, at a step downstream of opening hairpin-sealed coding ends. Thus, DNA-PKcs has critical functions in coding end joining beyond promoting Artemis endonuclease activity, and these functions can be regulated redundantly by the kinase activity of either ATM or DNA-PKcs.
    Keywords DNA ; alanine ; cell biology ; genes ; mutation ; phosphorylation ; protein kinases ; protein subunits ; threonine
    Language English
    Dates of publication 2013-0901
    Size p. 3568-3579.
    Publishing place Taylor & Francis
    Document type Article ; Online
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00308-13
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors.

    Borghesi, Lisa / Hsu, Lih-Yun / Miller, Juli P / Anderson, Michael / Herzenberg, Leonard / Herzenberg, Leonore / Schlissel, Mark S / Allman, David / Gerstein, Rachel M

    The Journal of experimental medicine

    2004  Volume 199, Issue 4, Page(s) 491–502

    Abstract: Expression of V(D)J recombinase activity in developing lymphocytes is absolutely required ... for initiation of V(D)J recombination at antigen receptor loci. However, little is known about when during ... hematopoietic development the V(D)J recombinase is first active, nor is it known what elements activate ...

    Abstract Expression of V(D)J recombinase activity in developing lymphocytes is absolutely required for initiation of V(D)J recombination at antigen receptor loci. However, little is known about when during hematopoietic development the V(D)J recombinase is first active, nor is it known what elements activate the recombinase in multipotent hematopoietic progenitors. Using mice that express a fluorescent transgenic V(D)J recombination reporter, we show that the V(D)J recombinase is active as early as common lymphoid progenitors (CLPs) but not in the upstream progenitors that retain myeloid lineage potential. Evidence of this recombinase activity is detectable in all four progeny lineages (B, T, and NK, and DC), and rag2 levels are the highest in progenitor subsets immediately downstream of the CLP. By single cell PCR, we demonstrate that V(D)J rearrangements are detectable at IgH loci in approximately 5% of splenic natural killer cells. Finally, we show that recombinase activity in CLPs is largely controlled by the Erag enhancer. As activity of the Erag enhancer is restricted to the B cell lineage, this provides the first molecular evidence for establishment of a lineage-specific transcription program in multipotent progenitors.
    MeSH term(s) Animals ; B-Lymphocytes/enzymology ; B-Lymphocytes/immunology ; Green Fluorescent Proteins ; Hematopoietic Stem Cells/enzymology ; Hematopoietic Stem Cells/immunology ; Homeodomain Proteins/genetics ; Luminescent Proteins/genetics ; Lymphopoiesis/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Polymerase Chain Reaction ; VDJ Recombinases/genetics ; VDJ Recombinases/metabolism
    Chemical Substances Homeodomain Proteins ; Luminescent Proteins ; RAG-1 protein (128559-51-3) ; Green Fluorescent Proteins (147336-22-9) ; VDJ Recombinases (EC 2.7.7.-)
    Language English
    Publishing date 2004-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20031800
    Database MEDical Literature Analysis and Retrieval System OnLINE

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