TY  - JOUR
AB  - Pf1, also known as Phf12 (plant homeodomain [PHD] zinc finger protein 12), is a member of the PHD zinc finger family of proteins. Pf1 associates with a chromatin-interacting protein complex comprised of MRG15, Sin3B, and histone deacetylase 1 (HDAC1) that functions as a transcriptional modulator. The biological function of Pf1 remains largely elusive. We undertook the generation of Pf1 knockout mice to elucidate its physiological role. We demonstrate that Pf1 is required for mid- to late gestation viability. Pf1 inactivation impairs the proliferative potential of mouse embryonic fibroblasts (MEFs) and is associated with a significant decrease in bromodeoxyuridine incorporation; an increase in senescence-associated β-galactosidase (SA-β-Gal) activity, a marker of cellular senescence; and elevated levels of phosphorylated H2AX (γ-H2A.X), a marker associated with DNA double-strand breaks. Analysis of transcripts differentially expressed in wild-type and Pf1-deficient cells revealed the impact of Pf1 in multiple regulatory arms of the ribosome biogenesis pathways. Strikingly, assessment of the morphology of the nucleoli exposed an abnormal nucleolar structure in Pf1-deficient cells. Finally, proteomic analysis of the Pf1-interacting complexes highlighted proteins involved in ribosome biogenesis. Taken together, our data reveal an unsuspected function for the Pf1-associated chromatin complex in the ribosomal biogenesis and senescence pathways.
AU  - Graveline, R.*
AU  - Marcinkiewicz, K.*
AU  - Choi, S.*
AU  - Paquet, M.*
AU  - Wurst, W.
AU  - Floss, T.
AU  - David, G.*
C1  - 50496
C2  - 40669
TI  - The chromatin associated Phf12 protein maintains nucleolar integrity and prevents premature cellular senescence.
JO  - Mol. Cell. Biol.
VL  - 37
IS  - 5
PY  - 2017
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Angiogenesis is a central regulator for white (WAT) and brown adipose tissue (BAT) adaptation in the course of obesity. Here we show that deletion of hypoxia-inducible factor 2α (HIF2α) in adipocytes (by using Fabp4-Cre transgenic mice), but not in myeloid or endothelial cells, negatively impacted on WAT angiogenesis and promoted WAT inflammation, WAT dysfunction, hepatosteatosis and systemic insulin resistance in obesity. Importantly, adipocyte HIF2α regulated vascular endothelial growth factor (VEGF) expression and angiogenesis of the obese BAT as well as its thermogenic function. Consistently, obese adipocyte-specific HIF2α-deficient mice displayed BAT dysregulation, associated with reduced levels of uncoupling protein-1 (UCP1) and a dysfunctional thermogenic response to cold exposure. VEGF administration reversed WAT and BAT inflammation and BAT dysfunction in adipocyte HIF2α-deficient mice. Together, adipocyte HIF2α is protective against maladaptation to obesity and metabolic dysregulation by promoting angiogenesis in both WAT and BAT and by counteracting obesity-mediated BAT dysfunction.
AU  - Garcia-Martin, R.*
AU  - Alexaki, V.I.*
AU  - Qin, N.*
AU  - Rubin de Celis, M.F.*
AU  - Economopoulou, M.*
AU  - Ziogas, A.*
AU  - Gercken, B.*
AU  - Kotlabova, K.*
AU  - Phieler, J.*
AU  - Ehrhart-Bornstein, M.*
AU  - Bornstein, S.R.
AU  - Eisenhofer, G.*
AU  - Breier, G.*
AU  - Blueher, M.*
AU  - Hampe, J.*
AU  - El-Armouche, A.*
AU  - Chatzigeorgiou, A.
AU  - Chung, K.-J.*
AU  - Chavakis, T.
C1  - 47816
C2  - 39555
SP  - 376-393
TI  - Adipocyte-specific hypoxia-inducible factor 2α deficiency exacerbates obesity-induced brown adipose tissue dysfunction and metabolic dysregulation.
JO  - Mol. Cell. Biol.
VL  - 36
IS  - 3
PY  - 2016
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including predicted C-terminal WD40 repeats. In this study we analyzed functional and molecular features conferred by the WD40 domain. Electron microscopic analysis of purified LRRK2 C-terminal domain revealed doughnut-shaped particles, providing experimental evidence for its WD40 fold. We demonstrate that LRRK2 WD40 binds and sequesters synaptic vesicle via interaction with vesicle-associated proteins. In fact, a domain-based pull-down approach combined with mass spectrometric analysis identified LRRK2 as being part of a highly specific protein network involved in synaptic vesicle trafficking. In addition, we found that a C-terminal sequence variant associated with an increased risk of developing PD, G2385R, correlates with a reduced binding affinity of LRRK2 WD40 to synaptic vesicles. Our data demonstrate a critical role of WD40 domain within LRRK2 function.
AU  - Piccoli, G.
AU  - Onofri, F.*
AU  - Cirnaru, M.D.*
AU  - Kaiser, C.J.*
AU  - Jagtap, P.K.
AU  - Kastenmüller, A.*
AU  - Pischedda, F.*
AU  - Marte, A.*
AU  - von Zweydorf, F.*
AU  - Vogt, A.
AU  - Giesert, F.
AU  - Pan, L.*
AU  - Antonucci, F.*
AU  - Kiel, C.*
AU  - Zhang, M.*
AU  - Weinkauf, S.*
AU  - Sattler, M.
AU  - Sala, C.*
AU  - Matteoli, M.*
AU  - Ueffing, M.
AU  - Gloeckner, C.J.
C1  - 30967
C2  - 34078
CY  - Washington
SP  - 2147-2161 
TI  - Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein interactions mediated by its C-terminal WD40 domain.
JO  - Mol. Cell. Biol.
VL  - 34
IS  - 12
PB  - Amer Soc Microbiology
PY  - 2014
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - ISWI is an evolutionarily conserved ATPase that catalyzes nucleosome remodeling in different macromolecular complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, are thought to have specialized functions despite their high sequence similarity. To date, the function of SNF2L in human cells has not been a focus of research. Newly established specific monoclonal antibodies and selective RNA interference protocols have now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. In contrast to earlier results, we found SNF2L to be broadly expressed in primary human tissues. Depletion of SNF2L in He La cells led to enhanced proliferation and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. Accordingly, high levels of SNF2L expression in normal melanocytes contrast with undetectable expression in malignant melanoma. In summary, our data document an inverse relationship between SNF2L expression and features characteristic of malignant cells.
AU  - Eckey, M.*
AU  - Kuphal, S.*
AU  - Straub, T.*
AU  - Rummele, P.*
AU  - Kremmer, E.
AU  - Bosserhoff, A.K.*
AU  - Becker, P.B.*
C1  - 7670
C2  - 29904
SP  - 2359-2371
TI  - Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.
JO  - Mol. Cell. Biol.
VL  - 32
IS  - 13
PB  - Amer. Soc. Microbiology
PY  - 2012
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Semaphorins and their receptors, plexins, are emerging as key regulators of various aspects of neural and nonneural development. Semaphorin 4D (Sema4D) and B-type plexins demonstrate distinct expression patterns over critical time windows during the development of the murine neocortex. Here, analysis of mice genetically lacking plexin-B1 or plexin-B2 revealed the significance of Sema4D-plexin-B signaling in cortical development. Deficiency of plexin-B2 resulted in abnormal cortical layering and defective migration and differentiation of several subtypes of cortical neurons, including Cajal-Retzius cells, GABAergic interneurons, and principal cells in vivo. In contrast, a lack of plexin-B1 did not impact on cortical development in vivo. In various ex vivo assays on embryonic forebrain, Sema4D enhanced the radial and tangential migration of developing neurons in a plexin-B2-dependent manner. These results suggest that Sema4D-plexin-B2 interactions regulate mechanisms underlying cell specification, differentiation, and migration during corticogenesis.
AU  - Hirschberg, A.*
AU  - Deng, S.*
AU  - Korostylev, A.*
AU  - Paldy, E.*
AU  - Costa, M.R.
AU  - Worzfeld, T.*
AU  - Vodrazka, P.*
AU  - Wizenmann, A.
AU  - Götz, M.
AU  - Offermanns, S.*
AU  - Kuner, R.*
C1  - 214
C2  - 27162
SP  - 764-780
TI  - Gene deletion mutants reveal a role for semaphorin receptors of the plexin-B family in mechanisms underlying corticogenesis.
JO  - Mol. Cell. Biol.
VL  - 30
IS  - 3
PB  - American Society for Microbiology
PY  - 2010
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Histone modifications play an important role in shaping chromatin structure. Here, we describe the use of an in vitro chromatin assembly system from Drosophila embryo extracts to investigate the dynamic changes of histone modifications subsequent to histone deposition. In accordance with what has been observed in vivo, we find a deacetylation of the initially diacetylated isoform of histone H4, which is dependent on chromatin assembly. Immediately after deposition of the histones onto DNA, H4 is monomethylated at K20, which is required for an efficient deacetylation of the H4 molecule. H4K20 methylation-dependent dl(3) MBT association with chromatin and the identification of a dl(3) MBT-dRPD3 complex suggest that a deacetylase is specifically recruited to the monomethylated substrate through interaction with dl(3) MBT. Our data demonstrate that histone modifications are added and removed during chromatin assembly in a highly regulated manner.
AU  - Scharf, A.N.*
AU  - Meier, K.*
AU  - Seitz, V.*
AU  - Kremmer, E.
AU  - Brehm, A.*
AU  - Imhof, A.*
C1  - 908
C2  - 25848
SP  - 57-67
TI  - Monomethylation of lysine 20 on histone H4 facilitates chromatin maturation.
JO  - Mol. Cell. Biol.
VL  - 29
IS  - 1
PB  - Amer Soc Microbiology
PY  - 2009
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Stabilin-1 is a unique scavenger receptor that combines endocytic and intracellular sorting functions in macrophages. Stabilin-1 mediates the endocytosis of acetylated low-density lipoprotein (acLDL), SPARC, and growth hormone family member placental lactogen (PL). At the same time, stabilin-1 is involved in trans-Golgi network-to-endosome routing of the endogenous chitinase-like protein SI-CLP (stabilin-interacting chitinase-like protein). A DDSLL motif in the cytoplasmic tail of stabilin-1 interacts with GGA adaptors; however, the deletion of DDSLL reduces but does not abrogate this interaction. Here, we identified a novel GGA-binding site, EDDADDD, in the cytoplasmic tail of stabilin-1. The deletion of EDDADDD impaired and the deletion of both the DDSLL and EDDADDD sites abrogated the interaction of stabilin-1 with GGAs. The surface exposure of stabilin-1 and stabilin-1-mediated endocytosis of acLDL, SPARC, and PL were not affected by the deletion either of DDSLL or EDDADDD or both. At the same time, both GGA-binding sites were necessary for the intracellular sorting of SI-CLP performed by stabilin-1. Our data indicate that the novel GGA-binding site EDDADDD is essential for stabilin-1-mediated intracellular sorting but is not required for endocytosis.
AU  - Zhang, J.*
AU  - Gratchev, A.*
AU  - Riabov, V.*
AU  - Mamidi, S.
AU  - Schmuttermaier, C.*
AU  - Krusell, L.*
AU  - Kremmer, E.
AU  - Workman, G.*
AU  - Sage, E.H.*
AU  - Jalkanen, S.*
AU  - Goerdt, S.*
AU  - Kzhyshkowska, J.*
C1  - 141
C2  - 26524
CY  - Washington
SP  - 6097-6105
TI  - A novel GGA-binding site is required for intracellular sorting mediated by stabilin-1.
JO  - Mol. Cell. Biol.
VL  - 29
IS  - 22
PB  - Amer Soc Microbiology
PY  - 2009
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - ATP-dependent chromatin remodelers of the CHD family play important roles during differentiation and development. Three CHD proteins, dMi-2, dChd1, and Kismet, have been described for Drosophila melanogaster. Here, we study dCHD3, a novel member of the CHD family. dCHD3 is related in sequence to dMi-2 but lacks several domains implicated in dMi-2 function. We demonstrate that dCHD3 is a nuclear protein and that expression is tightly regulated during fly development. Recombinant dCHD3 remodels mono- and polynucleosomes in an ATP-dependent manner in vitro. Its chromodomains are critical for nucleosome binding and remodeling. Unlike dMi-2, dCHD3 exists as a monomer. Nevertheless, both proteins colocalize with RNA polymerase II to actively transcribed regions on polytene chromosomes, suggesting that both remodelers participate in the process of transcription.
AU  - Murawska, M.*
AU  - Kunert, N.*
AU  - van Vugt, J.*
AU  - Längst, G.*
AU  - Kremmer, E.
AU  - Logie, C.*
AU  - Brehm, A.*
C1  - 4577
C2  - 25778
SP  - 2745-2757
TI  - dCHD3, a novel ATP-dependent chromatin remodeler associated with sites of active transcription.
JO  - Mol. Cell. Biol.
VL  - 28
IS  - 8
PB  - American Society for Microbiology
PY  - 2008
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Chicken DT40 cells deficient in the 9-1-1 checkpoint clamp exhibit hypersensitivity to a variety of DNA-damaging agents. Although recent work suggests that, in addition to its role in checkpoint activation, this complex may play a role in homologous recombination and translesion synthesis, the cause of this hypersensitivity has not been studied thoroughly. The immunoglobulin locus of DT40 cells allows monitoring of homologous recombination and translesion synthesis initiated by activation-induced deaminase (AID)-dependent abasic sites. We show that both the RAD9(-/-) and RAD17(-/-) mutants exhibit substantially reduced immunoglobulin gene conversion. However, the level of nontemplated immunoglobulin point mutation increased in these mutants, a finding that is reminiscent of the phenotype resulting from the loss of RAD51 paralogs or Brca2. This suggests that the 9-1-1 complex does not play a central role in translesion synthesis in this context. Despite reduced immunoglobulin gene conversion, the RAD9(-/-) and RAD17(-/-) cells do not exhibit a prominent defect in double-strand break-induced gene conversion or a sensitivity to camptothecin. This suggests that the roles of Rad9 and Rad17 may be confined to a subset of homologous recombination reactions initiated by replication-stalling lesions rather than those associated with double-strand break repair.
AU  - Saberi, A.*
AU  - Nakahara, M.*
AU  - Sale, J.E.*
AU  - Kikuchi, K.*
AU  - Arakawa, H.
AU  - Buerstedde, J.M.
AU  - Yamamoto, K.*
AU  - Takeda, S.*
AU  - Sonoda, E.*
C1  - 388
C2  - 25854
SP  - 6113-6122
TI  - The 9-1-1 DNA clamp is required for immunoglobulin gene conversion.
JO  - Mol. Cell. Biol.
VL  - 28
IS  - 19
PB  - American Society for Microbiology
PY  - 2008
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - The PeBoW complex is essential for cell proliferation and maturation of the large ribosomal subunit in mammalian cells. Here we examined the role of PeBoW-specific proteins Pes1, Bop1, and WDR12 in complex assembly and stability, nucleolar transport, and preribosome association. Recombinant expression of the three subunits is sufficient for complex formation. The stability of all three subunits strongly increases upon incorporation into the complex. Only overexpression of Bop1 inhibits cell proliferation and rRNA processing, and its negative effects could be rescued by coexpression of WDR12, but not Pes1. Elevated levels of Bop1 induce Bop1/WDR12 and Bop1/Pes1 subcomplexes. Knockdown of Bop1 abolishes the copurification of Pes1 with WDR12, demonstrating Bop1 as the integral component of the complex. Overexpressed Bop1 substitutes for endogenous Bop1 in PeBoW complex assembly, leading to the instability of endogenous Bop1. Finally, indirect immunofluorescence, cell fractionation, and sucrose gradient centrifugation experiments indicate that transport of Bop1 from the cytoplasm to the nucleolus is Pes1 dependent, while Pes1 can migrate to the nucleolus and bind to preribosomal particles independently of Bop1. We conclude that the assembly and integrity of the PeBoW complex are highly sensitive to changes in Bop1 protein levels.
AU  - Rohrmoser, M.
AU  - Hölzel, M.
AU  - Grimm, T.
AU  - Malamoussi, A.
AU  - Harasim, T.
AU  - Orban, M.
AU  - Pfisterer, P.*
AU  - Gruber-Eber, A.
AU  - Kremmer, E.
AU  - Eick, D.
C1  - 3525
C2  - 24416
SP  - 3682-3694
TI  - Interdependence of Pes1, Bop1, and WDR12 Controls Nucleolar Localization and Assembly of the PeBoW Complex Required for Maturation of the 60S Ribosomal Subunit.
JO  - Mol. Cell. Biol.
VL  - 27
IS  - 10
PB  - American Society for Microbiology
PY  - 2007
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - The Saccharomyces cerevisiae RAD18 gene is essential for postreplication repair but is not required for homologous recombination (HR), which is the major double-strand break (DSB) repair pathway in yeast. Accordingly, yeast rad18 mutants are tolerant of camptothecin (CPT), a topoisomerase I inhibitor, which induces DSBs by blocking replication. Surprisingly, mammalian cells and chicken DT40 cells deficient in Rad18 display reduced HR-dependent repair and are hypersensitive to CPT. Deletion of nonhomologous end joining (NHEJ), a major DSB repair pathway in vertebrates, in rad18-deficient DT40 cells completely restored HR-mediated DSB repair, suggesting that vertebrate Rad18 regulates the balance between NHEJ and HR. We previously reported that loss of NHEJ normalized the CPT sensitivity of cells deficient in poly(ADP-ribose) polymerase 1 (PARP1). Concomitant deletion of Rad18 and PARP1 synergistically increased CPT sensitivity, and additional inactivation of NHEJ normalized this hypersensitivity, indicating their parallel actions. In conclusion, higher-eukaryotic cells separately employ PARP1 and Rad18 to suppress the toxic effects of NHEJ during the HR reaction at stalled replication forks.
AU  - Saberi, A.*
AU  - Hochegger, H.*
AU  - Szuts, D.*
AU  - Lan, L.*
AU  - Yasui, A.*
AU  - Sale, J.E.*
AU  - Taniguchi, Y.*
AU  - Murakawa, Y.*
AU  - Zeng, W.*
AU  - Yokomori, K.*
AU  - Helleday, T.*
AU  - Teraoka, H.*
AU  - Arakawa, H.
AU  - Buerstedde, J.-M.
AU  - Takeda, S.*
C1  - 191
C2  - 24995
SP  - 2562-2571
TI  - RAD18 and poly(ADP-ribose) polymerase independently suppress the access of nonhomologous end joining to double-strand breaks and facilitate homologous recombination-mediated repair.
JO  - Mol. Cell. Biol.
VL  - 27
IS  - 7
PB  - merican Society for Microbiology
PY  - 2007
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Beekman, C.*
AU  - Nichane, M.*
AU  - de Clercq, S.*
AU  - Maetens, M.*
AU  - Floß, T.
AU  - Wurst, W.
AU  - Bellefroid, E.*
AU  - Marine, J.-C.*
C1  - 5109
C2  - 24143
SP  - 9291-9301
TI  - Evolutionarily conserved role of nucleostemin: Controlling proliferation of stem/progenitor cells during early vertebrate development.
JO  - Mol. Cell. Biol.
VL  - 26
PY  - 2006
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity
AU  - del Barco Barrantes, I.*
AU  - Montero-Pedrazuela, A.*
AU  - Guadano-Ferraz, A.*
AU  - Obregon, M.J.*
AU  - de Mena, R.M.*
AU  - Gailus-Durner, V.
AU  - Fuchs, H.
AU  - Franz, T.J.*
AU  - Kalaydjiev, S.*
AU  - Klempt, M.*
AU  - Hölter, S.M.
AU  - Rathkolb, B.*
AU  - Reinhard, C.
AU  - de Escobar, G.M.*
AU  - Bernal, J.*
AU  - Busch, D.H.*
AU  - Wurst, W.
AU  - Wolf, E.*
AU  - Schulz, S.
AU  - Shtrom, S.*
AU  - Greiner, E.*
AU  - Hrabě de Angelis, M.
AU  - Westphal, H.*
AU  - Niehrs, C.*
C1  - 4008
C2  - 23541
SP  - 2317-2326
TI  - Generation and characterization of dickkopf3 mutant mice.
JO  - Mol. Cell. Biol.
VL  - 26
IS  - 6
PY  - 2006
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Gerhardt, J.
AU  - Jafar, S.
AU  - Spindler, M.-P.
AU  - Ott, E.
AU  - Schepers, A.
C1  - 4463
C2  - 23998
SP  - 7731-7746
TI  - Identification of new human origins of DNA replication by an origin-trapping assay.
JO  - Mol. Cell. Biol.
VL  - 26
PY  - 2006
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Ghosh, M.*
AU  - Kemp, M.*
AU  - Liu, G.*
AU  - Ritzi, M.*
AU  - Schepers, A.
AU  - Leffak, M.*
C1  - 2680
C2  - 24151
SP  - 5270-5283
TI  - Differential binding of replication proteins across the human c-myc replicator.
JO  - Mol. Cell. Biol.
VL  - 26
PY  - 2006
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Grad, I.*
AU  - McKee, T.A.*
AU  - Ludwig, S.M.*
AU  - Hoyle, G.W.*
AU  - Ruiz, P.*
AU  - Wurst, W.
AU  - Floß, T.
AU  - Miller, C.A.*
AU  - Picard, D.*
C1  - 5108
C2  - 24141
SP  - 8976-8983
TI  - The Hsp90 cochaperone p23 is essential for perinatal survival.
JO  - Mol. Cell. Biol.
VL  - 26
PY  - 2006
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Hauck, S.M.
AU  - Kinkl, N.
AU  - Deeg, C.A.*
AU  - Swiatek-de Lange, M.
AU  - Schöffmann, S.
AU  - Ueffing, M.
C1  - 2177
C2  - 23626
SP  - 2746-2757
TI  - GDNF family ligands trigger indirect neuroprotective signaling in retinal glial cells.
JO  - Mol. Cell. Biol.
VL  - 26
PY  - 2006
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Homologous recombination is a versatile DNA damage repair pathway requiring Rad51 and Rad54. Here we show that a mammalian Rad54 paralog, Rad54B, displays physical and functional interactions with Rad51 and DNA that are similar to those of Rad54. While ablation of Rad54 in mouse embryonic stem (ES) cells leads to a mild reduction in homologous recombination efficiency, the absence of Rad54B has little effect. However, the absence of both Rad54 and Rad54B dramatically reduces homologous recombination efficiency. Furthermore, we show that Rad54B protects ES cells from ionizing radiation and the interstrand DNA cross-linking agent mitomycin C. Interestingly, at the ES cell level the paralogs do not display an additive or synergic interaction with respect to mitomycin C sensitivity, yet animals lacking both Rad54 and Rad54B are dramatically sensitized to mitomycin C compared to either single mutant. This suggests that the paralogs possibly function in a tissue-specific manner. Finally, we show that Rad54, but not Rad54B, is needed for a normal distribution of Rad51 on meiotic chromosomes. Thus, even though the paralogs have similar biochemical properties, genetic analysis in mice uncovered their nonoverlapping roles. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
AU  - Wesoly, J.*
AU  - Agarwal, S.*
AU  - Sigurdsson, S.*
AU  - Bussen, W.*
AU  - van Komen, S.*
AU  - Qin, J.*
AU  - van Steeg, H.*
AU  - van Benthem, J.*
AU  - Wassenaar, E.*
AU  - Baarends, W.M.*
AU  - Ghazvini, M.*
AU  - Tafel, A.A.*
AU  - Heath, H.*
AU  - Galjart, N.*
AU  - Essers, J.*
AU  - Grootegoed, J.A.*
AU  - Arnheim, N.*
AU  - Bezzubova, O.
AU  - Buerstedde, J.M.
AU  - Sung, P.*
AU  - Kanaar, R.*
C1  - 1762
C2  - 24148
SP  - 976-989
TI  - Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair and meiosis.
JO  - Mol. Cell. Biol.
VL  - 26
IS  - 3
PY  - 2006
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Chapman, R.D.
AU  - Conrad, M.
AU  - Eick, D.
C1  - 2832
C2  - 22825
SP  - 7665-7674
TI  - Role of the mammalian RNA polymerase II C-terminal domain (CTD) nonconsensus repeats in CTD stability and cell proliferation.
JO  - Mol. Cell. Biol.
VL  - 25
PY  - 2005
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Conrad, M.
AU  - Moreno, S.G.
AU  - Sinowatz, F.*
AU  - Ursini, F.*
AU  - Kölle, S.*
AU  - Roveri, A.*
AU  - Brielmeier, M.
AU  - Wurst, W.
AU  - Maiorino, M.*
AU  - Bornkamm, G.W.
C1  - 1995
C2  - 22812
SP  - 7637-7644
TI  - The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability.
JO  - Mol. Cell. Biol.
VL  - 25
PY  - 2005
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - Two distinct thioredoxin/thioredoxin reductase systems are present in the cytosol and the mitochondria of mammalian cells. Thioredoxins (Txn), the main substrates of thioredoxin reductases (Txnrd), are involved in numerous physiological processes, including cell-cell communication, redox metabolism, proliferation, and apoptosis. To investigate the individual contribution of mitochondrial (Txnrd2) and cytoplasmic (Txnrd1) thioredoxin reductases in vivo, we generated a mouse strain with a conditionally targeted deletion of Txnrd1. We show here that the ubiquitous Cre-mediated inactivation of Txnrd1 leads to early embryonic lethality. Homozygous mutant embryos display severe growth retardation and fail to turn. In accordance with the observed growth impairment in vivo, Txnrd1-deficient embryonic fibroblasts do not proliferate in vitro. In contrast, ex vivo-cultured embryonic Txnrd1-deficient cardiomyocytes are not affected, and mice with a heart-specific inactivation of Txnrd1 develop normally and appear healthy. Our results indicate that Txnrd1 plays an essential role during embryogenesis in most developing tissues except the heart.
AU  - Jakupoglu, C.
AU  - Przemeck, G.K.H.
AU  - Schneider, M.
AU  - Moreno, S.G.
AU  - Mayr, N.
AU  - Hatzopoulos, A.K.
AU  - Hrabě de Angelis, M.
AU  - Wurst, W.
AU  - Bornkamm, G.W.
AU  - Brielmeier, M.
AU  - Conrad, M.
C1  - 4636
C2  - 22516
SP  - 1980-1988
TI  - Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development.
JO  - Mol. Cell. Biol.
VL  - 25
IS  - 5
PY  - 2005
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Yamamoto, K.*
AU  - Arakawa, H.
AU  - Buerstedde, J.-M.
C1  - 1505
C2  - 22570
SP  - 34-43
TI  - Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination.
JO  - Mol. Cell. Biol.
VL  - 25
PY  - 2005
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Conrad, M.
AU  - Jakupoglu, C.
AU  - Moreno, S.G.
AU  - Lippl, S.
AU  - Banjac, A.
AU  - Schneider, M.
AU  - Beck, H.
AU  - Hatzopoulos, A.K.
AU  - Just, U.
AU  - Sinowatz, F.*
AU  - Schmahl, W.*
C1  - 3447
C2  - 22191
SP  - 9414-9423
TI  - Essential role for mitochondrial thioredoxin reductase in hematopoisis, heart development and heart function.
JO  - Mol. Cell. Biol.
VL  - 24
PY  - 2004
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Fukuda, A.*
AU  - Nakadai, T.*
AU  - Shimada, M.*
AU  - Tsukui, T.*
AU  - Matsumoto, M.*
AU  - Nogi, Y.*
AU  - Meisterernst, M.
AU  - Hisatake, K.*
C1  - 5208
C2  - 22344
SP  - 6525-6535
TI  - Transcriptional coactivator PC4 stimulates promoter escape and facilitates transcriptional synergy by GAL4-VP16.
JO  - Mol. Cell. Biol.
VL  - 24
PY  - 2004
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Ishiai, M.*
AU  - Kimura, M.*
AU  - Namikoshi, K.*
AU  - Yamazoe, M.*
AU  - Yamamoto, K.*
AU  - Arakawa, H.
AU  - Agematsu, K.*
AU  - Matsushita, N.*
AU  - Takeda, S.*
AU  - Buerstedde, J.-M.
AU  - Takata, M.*
C1  - 3438
C2  - 22230
SP  - 10733-10741
TI  - DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation.
JO  - Mol. Cell. Biol.
VL  - 24
PY  - 2004
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Klejman, M.P.*
AU  - Pereira, L.A.*
AU  - van Zeeburg, H.J.T.*
AU  - Gilfillan, S.
AU  - Meisterernst, M.
AU  - Timmers, H.T.M.*
C1  - 2791
C2  - 22345
SP  - 10072-10082
TI  - NC2alpha interacts with BTAF1 and stimulates its ATP-dependent association with TATA-binding protein.
JO  - Mol. Cell. Biol.
VL  - 24
PY  - 2004
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Rodrigo, I.*
AU  - Bovolenta, P.*
AU  - Mankoo, B.S.*
AU  - Imai, K.
C1  - 3367
C2  - 22321
SP  - 2757-2766
TI  - Meox homeodomain proteins are required for Bapx1 expression in the sclerotome and activate its transcription by direct binding to its promoter.
JO  - Mol. Cell. Biol.
VL  - 24
PY  - 2004
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Gwack, Y.*
AU  - Baek, H.J.*
AU  - Nakamura, H.*
AU  - Lee, S.H.*
AU  - Meisterernst, M.
AU  - Roeder, R.G.*
AU  - Jung, J.U.*
C1  - 22382
C2  - 21297
SP  - 2055-2067
TI  - Principal Role a TRAP/Mediator and SWI/SNF Complexes in Kaposi's Sarcoma-Associated  Herpesvirus RTA-Mediated Lytic Reactivation.
JO  - Mol. Cell. Biol.
VL  - 23
PY  - 2003
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Yamamoto, K.*
AU  - Ishiai, M.*
AU  - Matsushita, N.*
AU  - Arakawa, H.
AU  - Lamerdin, J.E.*
AU  - Buerstedde, J.-M.
AU  - Tanimoto, M.*
AU  - Harada, M.*
AU  - Thompson, L.H.*
AU  - Takata, M.*
C1  - 9993
C2  - 21735
SP  - 5421-5430
TI  - Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells. 
JO  - Mol. Cell. Biol.
VL  - 23
PY  - 2003
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Schäffer, M.
AU  - Schneiderbauer, M.
AU  - Weidler, S.
AU  - Tavares, R.
AU  - Warmuth, M.
AU  - de Vos, G.
AU  - Hallek, M.
C1  - 22028
C2  - 20597
SP  - 8068-8081
TI  - Signaling through a Novel Domain of gp130 Mediates Cell Proliferation and Activation of Hck and Erk Kinases.
JO  - Mol. Cell. Biol.
VL  - 21
PY  - 2001
SN  - 0270-7306
ER  - 

TY  - JOUR
AB  - The Drosophila gap gene knirps (kni) is required for abdominal segmentation. It encodes a steroid/thyroid orphan receptor-type transcription factor which is distributed in a broad band of nuclei in the posterior region of the blastoderm. To identify essential domains of the kni protein (KNI), we cloned and sequenced the DNA encompassing the coding region of nine kni mutant alleles of different strength and kni-homologous genes of related insect species. We also examined in vitro-modified versions of KNI in various assay system both in vitro and in tissue culture. The results show that KNI contains several functional domains which are arranged in a modular fashion. The N-terminal 185-amino-acid region which includes the DNA-binding domain and a functional nuclear location signal fails to provide kni activity to the embryo. However, a truncated KNI protein that contains additional 47 amino acids exerts rather strong kni activity which is functionally defined by a weak kni mutant phenotype of the embryo. The additional 47-amino-acid stretch includes a transcriptional repressor domain which acts in the context of a heterologous DNA-binding domain of the yeast transcriptional activator GAL4. The different domains of KNI as defined by functional studies are conserved during insect evolution.
AU  - Gerwin, N.*
AU  - La Rosée, A.*
AU  - Sauer, F.A.*
AU  - Halbritter, H.P.*
AU  - Neumann, M.C.
AU  - Jäckle, H.*
AU  - Nauber, U.*
C1  - 40014
C2  - 38063
SP  - 7899-7908
TI  - Functional and conserved domains of the Drosophila transcription factor encoded by the segmentation gene knirps.
JO  - Mol. Cell. Biol.
VL  - 14
IS  - 12
PY  - 1994
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Henglein, B.
AU  - Chenivesse, X.
AU  - Wang, J.
AU  - Eick, D.
AU  - Bréchot, C.
C1  - 20101
C2  - 13276
TI  - Structure and Promoter Function of their Human Cyclin A Gene.
JO  - Mol. Cell. Biol.
PY  - 1994
SN  - 0270-7306
ER  - 

TY  - JOUR
AU  - Henglein, B.
AU  - Synovzik, H.
AU  - Groitl, P.
AU  - Bornkamm, G.W.
AU  - Hartl, P.
AU  - Lipp, M.
C1  - 19274
C2  - 12347
SP  - 2105-2113
TI  - Three Breakpoints of Variant t(2;8) Translocations in Burkitt's Lymphoma Cells Fall within a Region 140 Kilobases Distal from c-myc.
JO  - Mol. Cell. Biol.
VL  - 9
PY  - 1989
SN  - 0270-7306
ER  -