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101.
Jon M. Sutton David E. Clark Stephen J. Dunsdon Garry Fenton Amanda Fillmore Neil V. Harris Chris Higgs Chris A. Hurley Sussie L. Krintel Robert E. MacKenzie Alokesh Duttaroy Eric Gangl Wiesia Maniara Richard Sedrani Kenji Namoto Nils Ostermann Bernd Gerhartz Finton Sirockin Jörg Trappe Ulrich Hassiepen Daniel K. Baeschlin 《Bioorganic & medicinal chemistry letters》2012,22(6):2359
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104.
The replicative helicase MCM recruits cohesin acetyltransferase ESCO2 to mediate centromeric sister chromatid cohesion 下载免费PDF全文
Miroslav P Ivanov Rene Ladurner Ina Poser Rebecca Beveridge Evelyn Rampler Otto Hudecz Maria Novatchkova Jean‐Karim Hériché Gordana Wutz Petra van der Lelij Emanuel Kreidl James RA Hutchins Heinz Axelsson‐Ekker Jan Ellenberg Anthony A Hyman Karl Mechtler Jan‐Michael Peters 《The EMBO journal》2018,37(15)
Chromosome segregation depends on sister chromatid cohesion which is established by cohesin during DNA replication. Cohesive cohesin complexes become acetylated to prevent their precocious release by WAPL before cells have reached mitosis. To obtain insight into how DNA replication, cohesion establishment and cohesin acetylation are coordinated, we analysed the interaction partners of 55 human proteins implicated in these processes by mass spectrometry. This proteomic screen revealed that on chromatin the cohesin acetyltransferase ESCO2 associates with the MCM2‐7 subcomplex of the replicative Cdc45‐MCM‐GINS helicase. The analysis of ESCO2 mutants defective in MCM binding indicates that these interactions are required for proper recruitment of ESCO2 to chromatin, cohesin acetylation during DNA replication, and centromeric cohesion. We propose that MCM binding enables ESCO2 to travel with replisomes to acetylate cohesive cohesin complexes in the vicinity of replication forks so that these complexes can be protected from precocious release by WAPL. Our results also indicate that ESCO1 and ESCO2 have distinct functions in maintaining cohesion between chromosome arms and centromeres, respectively. 相似文献
105.
Natasha Fillmore Alda Huqi Jagdip S. Jaswal Jun Mori Roxane Paulin Alois Haromy Arzu Onay-Besikci Lavinia Ionescu Bernard Thébaud Evangelos Michelakis Gary D. Lopaschuk 《PloS one》2015,10(3)
Successful stem cell therapy requires the optimal proliferation, engraftment, and differentiation of stem cells into the desired cell lineage of tissues. However, stem cell therapy clinical trials to date have had limited success, suggesting that a better understanding of stem cell biology is needed. This includes a better understanding of stem cell energy metabolism because of the importance of energy metabolism in stem cell proliferation and differentiation. We report here the first direct evidence that human bone marrow mesenchymal stem cell (BMMSC) energy metabolism is highly glycolytic with low rates of mitochondrial oxidative metabolism. The contribution of glycolysis to ATP production is greater than 97% in undifferentiated BMMSCs, while glucose and fatty acid oxidation combined only contribute 3% of ATP production. We also assessed the effect of physiological levels of fatty acids on human BMMSC survival and energy metabolism. We found that the saturated fatty acid palmitate induces BMMSC apoptosis and decreases proliferation, an effect prevented by the unsaturated fatty acid oleate. Interestingly, chronic exposure of human BMMSCs to physiological levels of palmitate (for 24 hr) reduces palmitate oxidation rates. This decrease in palmitate oxidation is prevented by chronic exposure of the BMMSCs to oleate. These results suggest that reducing saturated fatty acid oxidation can decrease human BMMSC proliferation and cause cell death. These results also suggest that saturated fatty acids may be involved in the long-term impairment of BMMSC survival in vivo. 相似文献
106.
eae36, a locus on mouse chromosome 4, controls susceptibility to experimental allergic encephalomyelitis in older mice and mice immunized in the winter 下载免费PDF全文
Genetic factors are believed to contribute to multiple sclerosis (MS) susceptibility; however, strong evidence implicating intrinsic and environmental factors in the etiopathogenesis of MS also exists. Susceptibility to experimental allergic encephalomyelitis (EAE), the principal animal model of MS, is also influenced by nongenetic factors, including age and season at immunization. This suggests that age- and season-by-gene interactions exist and that different susceptibility loci may influence disease as a function of the two parameters. In this study, linkage analysis based on genome exclusion mapping was carried out using age and season at immunization restricted cohorts of (B10.S x SJL/J) F2 intercross mice in an effort to identify such linkages. Significant linkage of EAE to eae4 and eae5 was detected with 6- to 12-week-old and summer cohorts. In contrast, significant linkage of EAE to eae4 and eae5 was not detected with the >12-week-old and winter/spring populations. Rather, significant linkage to D4Mit203 at 128.50 Mb on chromosome 4 was detected with animals that were >12 weeks old at the time of immunization or were immunized in the winter. This previously unidentified locus has been designated eae36. These results support the existence of age- and season-by-gene-specific interactions in the genetic control of susceptibility to autoimmune inflammatory disease of the central nervous system and suggest that late-onset MS may be immunogenetically distinct. 相似文献
107.
Thomson DM Brown JD Fillmore N Condon BM Kim HJ Barrow JR Winder WW 《American journal of physiology. Endocrinology and metabolism》2007,293(6):E1572-E1579
5'-AMP-activated protein kinase (AMPK), by way of its inhibition of acetyl-CoA carboxylase (ACC), plays an important role in regulating malonyl-CoA levels and the rate of fatty acid oxidation in skeletal and cardiac muscle. In these tissues, LKB1 is the major AMPK kinase and is therefore critical for AMPK activation. The purpose of this study was to determine how the lack of muscle LKB1 would affect malonyl-CoA levels and/or fatty-acid oxidation. Comparing wild-type (WT) and skeletal/cardiac muscle-specific LKB1 knockout (KO) mice, we found that the 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)-stimulated decrease in malonyl-CoA levels in WT heart and quadriceps muscles was entirely dependent on the presence of LKB1, as was the AICAR-induced increase in fatty-acid oxidation in EDL muscles in vitro, since these responses were not observed in KO mice. Likewise, the decrease in malonyl-CoA levels after muscle contraction was attenuated in KO gastrocnemius muscles, suggesting that LKB1 plays an important role in promoting the inhibition of ACC, likely by activation of AMPK. However, since ACC phosphorylation still increased and malonyl-CoA levels decreased in KO muscles (albeit not to the levels observed in WT mice), whereas AMPK phosphorylation was entirely unresponsive, LKB1/AMPK signaling cannot be considered the sole mechanism for inhibiting ACC during and after muscle activity. Regardless, our results suggest that LKB1 is an important regulator of malonyl-CoA levels and fatty acid oxidation in skeletal muscle. 相似文献
108.
Zacharek SJ Fillmore CM Lau AN Gludish DW Chou A Ho JW Zamponi R Gazit R Bock C Jäger N Smith ZD Kim TM Saunders AH Wong J Lee JH Roach RR Rossi DJ Meissner A Gimelbrant AA Park PJ Kim CF 《Cell Stem Cell》2011,9(3):272-281
BMI1 is required for the self-renewal of stem cells in many tissues including the lung epithelial stem cells, Bronchioalveolar Stem Cells (BASCs). Imprinted genes, which exhibit expression from only the maternally or paternally inherited allele, are known to regulate developmental processes, but what their role is in adult cells remains a fundamental question. Many imprinted genes were derepressed in Bmi1 knockout mice, and knockdown of Cdkn1c (p57) and other imprinted genes partially rescued the self-renewal defect of Bmi1 mutant lung cells. Expression of p57 and other imprinted genes was required for lung cell self-renewal in culture and correlated with repair of lung epithelial cell injury in vivo. Our data suggest that BMI1-dependent regulation of expressed alleles at imprinted loci, distinct from imprinting per se, is required for control of lung stem cells. We anticipate that the regulation and function of imprinted genes is crucial for self-renewal in diverse adult tissue-specific stem cells. 相似文献
109.
Camarodont sea urchins possess a rapidly evolving actin gene family whose
members are expressed in distinct cell lineages in a developmentally
regulated fashion. Evolutionary changes in the actin gene family of
echinoids include alterations in number of family members, site of
expression, and gene linkage, and a dichotomy between rapidly and slowly
evolving isoform-specific 3' untranslated regions. We present sequence
comparisons and an analysis of the actin gene family in two congeneric sea
urchins that develop in radically different modes, Heliocidaris
erythrogramma and H. tuberculata. The sequences of several actin genes from
the related species Lytechinus variegatus are also presented. We compare
the features of the Heliocidaris and Lytechinus actin genes to those of the
the actin gene families of other closely related sea urchins and discuss
the nature of the evolutionary changes among sea urchin actins and their
relationship to developmental mode.
相似文献
110.
The phytochrome gene family in grasses (Poaceae): a phylogeny and evidence that grasses have a subset of the loci found in dicot angiosperms 总被引:13,自引:2,他引:11
The phytochrome nuclear gene family encodes photoreceptor proteins that
mediate developmental responses to red and far red light throughout the
life of the plant. From studies of the dicot flowering plant Arabidopsis,
the family has been modeled as comprising five loci, PHYA- PHYE. However,
it has been shown recently that the Arabidopsis model may not completely
represent some flowering plant groups because additional PHY loci related
to PHYA and PHYB of Arabidopsis apparently have evolved independently
several times in dicots, and monocot flowering plants may lack orthologs of
PHYD and PHYE of Arabidopsis. Nonetheless, the phytochrome nucleotide data
were informative in a study of organismal evolution because the loci occur
as single copy sequences and appear to be evolving independently. We have
continued our investigation of the phytochrome gene family in flowering
plants by sampling extensively in the grass family. The phytochrome nuclear
DNA data were cladistically analyzed to address the following questions:
(1) Are the data consistent with a pattern of differential distribution of
phytochrome genes among monocots and higher dicots, with homologs of PHYA,
B, C, D, and E present in higher dicots, but of just PHYA, B, and C in
monocots, and (2) what phylogenetic pattern within Poaceae do they reveal?
Results of these analyses, and of Southern blot experiments, are consistent
with the observation that the phytochrome gene family in grasses comprises
the same subset of loci detected in other monocots. Furthermore, for
studies of organismal phylogeny in the grass family, the data are shown to
provide significant support for relationships that are just weakly resolved
by other data sets.
相似文献