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Molecular Cell

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https://www.readbyqxmd.com/read/27916661/tetrameric-assembly-of-k-channels-requires-er-located-chaperone-proteins
#1
Kai Li, Qiang Jiang, Xue Bai, Yi-Feng Yang, Mei-Yu Ruan, Shi-Qing Cai
Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K(+) channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K(+) channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4...
November 30, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27916662/acetylation-of-pcna-sliding-surface-by-eco1-promotes-genome-stability-through-homologous-recombination
#2
Pierre Billon, Jian Li, Jean-Philippe Lambert, Yizhang Chen, Véronique Tremblay, Joseph S Brunzelle, Anne-Claude Gingras, Alain Verreault, Tomohiko Sugiyama, Jean-Francois Couture, Jacques Côté
During DNA replication, proliferating cell nuclear antigen (PCNA) adopts a ring-shaped structure to promote processive DNA synthesis, acting as a sliding clamp for polymerases. Known posttranslational modifications function at the outer surface of the PCNA ring to favor DNA damage bypass. Here, we demonstrate that acetylation of lysine residues at the inner surface of PCNA is induced by DNA lesions. We show that cohesin acetyltransferase Eco1 targets lysine 20 at the sliding surface of the PCNA ring in vitro and in vivo in response to DNA damage...
November 16, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27867010/quorum-sensing-controls-adaptive-immunity-through-the-regulation-of-multiple-crispr-cas-systems
#3
Adrian G Patterson, Simon A Jackson, Corinda Taylor, Gary B Evans, George P C Salmond, Rita Przybilski, Raymond H J Staals, Peter C Fineran
Bacteria commonly exist in high cell density populations, making them prone to viral predation and horizontal gene transfer (HGT) through transformation and conjugation. To combat these invaders, bacteria possess an arsenal of defenses, such as CRISPR-Cas adaptive immunity. Many bacterial populations coordinate their behavior as cell density increases, using quorum sensing (QS) signaling. In this study, we demonstrate that QS regulation results in increased expression of the type I-E, I-F, and III-A CRISPR-Cas systems in Serratia cells in high-density populations...
November 16, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27867008/molecular-structures-of-transcribing-rna-polymerase-i
#4
Lucas Tafur, Yashar Sadian, Niklas A Hoffmann, Arjen J Jakobi, Rene Wetzel, Wim J H Hagen, Carsten Sachse, Christoph W Müller
RNA polymerase I (Pol I) is a 14-subunit enzyme that solely synthesizes pre-ribosomal RNA. Recently, the crystal structure of apo Pol I gave unprecedented insight into its molecular architecture. Here, we present three cryo-EM structures of elongating Pol I, two at 4.0 Å and one at 4.6 Å resolution, and a Pol I open complex at 3.8 Å resolution. Two modules in Pol I mediate the narrowing of the DNA-binding cleft by closing the clamp domain. The DNA is bound by the clamp head and by the protrusion domain, allowing visualization of the upstream and downstream DNA duplexes in one of the elongation complexes...
November 16, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27916660/isoform-switch-of-tet1-regulates-dna-demethylation-and-mouse-development
#5
Wenhao Zhang, Weikun Xia, Qiujun Wang, Aaron J Towers, Jiayu Chen, Rui Gao, Yu Zhang, Chia-An Yen, Ah Young Lee, Yuanyuan Li, Chen Zhou, Kaili Liu, Jing Zhang, Tian-Peng Gu, Xiuqi Chen, Zai Chang, Danny Leung, Shaorong Gao, Yong-Hui Jiang, Wei Xie
The methylcytosine oxidase TET proteins play important roles in DNA demethylation and development. However, it remains elusive how exactly they target substrates and execute oxidation. Interestingly, we found that, in mice, the full-length TET1 isoform (TET1e) is restricted to early embryos, embryonic stem cells (ESCs), and primordial germ cells (PGCs). By contrast, a short isoform (TET1s) is preferentially expressed in somatic cells, which lacks the N terminus including the CXXC domain, a DNA-binding module that often recognizes CpG islands (CGIs) where TET1 predominantly occupies...
November 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27889453/simultaneous-real-time-imaging-of-leading-and-lagging-strand-synthesis-reveals-the-coordination-dynamics-of-single-replisomes
#6
Karl E Duderstadt, Hylkje J Geertsema, Sarah A Stratmann, Christiaan M Punter, Arkadiusz W Kulczyk, Charles C Richardson, Antoine M van Oijen
The molecular machinery responsible for DNA replication, the replisome, must efficiently coordinate DNA unwinding with priming and synthesis to complete duplication of both strands. Due to the anti-parallel nature of DNA, the leading strand is copied continuously, while the lagging strand is produced by repeated cycles of priming, DNA looping, and Okazaki-fragment synthesis. Here, we report a multidimensional single-molecule approach to visualize this coordination in the bacteriophage T7 replisome by simultaneously monitoring the kinetics of loop growth and leading-strand synthesis...
November 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27889452/an-rb-ezh2-complex-mediates-silencing-of-repetitive-dna-sequences
#7
Charles A Ishak, Aren E Marshall, Daniel T Passos, Carlee R White, Seung J Kim, Matthew J Cecchini, Sara Ferwati, William A MacDonald, Christopher J Howlett, Ian D Welch, Seth M Rubin, Mellissa R W Mann, Frederick A Dick
Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments...
November 12, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27867007/srf-co-factors-control-the-balance-between-cell-proliferation-and-contractility
#8
Francesco Gualdrini, Cyril Esnault, Stuart Horswell, Aengus Stewart, Nik Matthews, Richard Treisman
The ERK-regulated ternary complex factors (TCFs) act with the transcription factor serum response factor (SRF) to activate mitogen-induced transcription. However, the extent of their involvement in the immediate-early transcriptional response, and their wider functional significance, has remained unclear. We show that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible gene transcription and impairs cell proliferation. Using integrated SRF ChIP-seq and Hi-C data, we identified over 700 TCF-dependent SRF direct target genes involved in signaling, transcription, and proliferation...
November 5, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27773676/the-structures-of-eif4e-eif4g-complexes-reveal-an-extended-interface-to-regulate-translation-initiation
#9
Stefan Grüner, Daniel Peter, Ramona Weber, Lara Wohlbold, Min-Yi Chung, Oliver Weichenrieder, Eugene Valkov, Cátia Igreja, Elisa Izaurralde
Eukaryotic initiation factor 4G (eIF4G) plays a central role in translation initiation through its interactions with the cap-binding protein eIF4E. This interaction is a major drug target for repressing translation and is naturally regulated by 4E-binding proteins (4E-BPs). 4E-BPs and eIF4G compete for binding to the eIF4E dorsal surface via a shared canonical 4E-binding motif, but also contain auxiliary eIF4E-binding sequences, which were assumed to contact non-overlapping eIF4E surfaces. However, it is unknown how metazoan eIF4G auxiliary sequences bind eIF4E...
October 19, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27773677/tail-and-kinase-modules-differently-regulate-core-mediator-recruitment-and-function-in%C3%A2-vivo
#10
Célia Jeronimo, Marie-France Langelier, Alain R Bataille, John M Pascal, B Franklin Pugh, François Robert
Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM). Previous work suggests regulatory roles for Tail and CKM, but an integrated model for these activities is lacking. Here, we analyzed the genome-wide distribution of Mediator subunits in wild-type and mutant yeast cells in which RNA polymerase II promoter escape is blocked, allowing detection of transient Mediator forms. We found that although all modules are recruited to upstream activated regions (UAS), assembly of Mediator within the pre-initiation complex is accompanied by the release of CKM...
October 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27746019/reducing-ribosome-biosynthesis-promotes-translation-during-low-mg-2-stress
#11
Mauricio H Pontes, Jinki Yeom, Eduardo A Groisman
The synthesis of ribosomes is regulated by both amino acid abundance and the availability of ATP, which regenerates guanosine triphosphate (GTP), powers ribosomes, and promotes transcription of rRNA genes. We now report that bacteria supersede both of these controls when experiencing low cytosolic magnesium (Mg(2+)), a divalent cation essential for ribosome stabilization and for neutralization of ATP's negative charge. We uncover a regulatory circuit that responds to low cytosolic Mg(2+) by promoting expression of proteins that import Mg(2+) and lower ATP amounts...
October 8, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27773673/polo-like-kinase-1-regulates-myc-stabilization-and-activates-a-feedforward-circuit-promoting-tumor-cell-survival
#12
Daibiao Xiao, Ming Yue, Hexiu Su, Ping Ren, Jue Jiang, Feng Li, Yufeng Hu, Haining Du, Hudan Liu, Guoliang Qing
MYCN amplification in human cancers predicts poor prognosis and resistance to therapy. However, pharmacological strategies that directly target N-Myc, the protein encoded by MYCN, remain elusive. Here, we identify a molecular mechanism responsible for reciprocal activation between Polo-like kinase-1 (PLK1) and N-Myc. PLK1 specifically binds to the SCF(Fbw7) ubiquitin ligase, phosphorylates it, and promotes its autopolyubiquitination and proteasomal degradation, counteracting Fbw7-mediated degradation of N-Myc and additional substrates, including cyclin E and Mcl1...
October 4, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912098/characterization-of-hippo-pathway-components-by-gene-inactivation
#13
Steven W Plouffe, Zhipeng Meng, Kimberly C Lin, Brian Lin, Audrey W Hong, Justin V Chun, Kun-Liang Guan
The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well understood how the Hippo pathway becomes dysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912097/lncpress1-is-a-p53-regulated-lncrna-that-safeguards-pluripotency-by-disrupting-sirt6-mediated-de-acetylation-of-histone-h3k56
#14
Abhinav K Jain, Yuanxin Xi, Ryan McCarthy, Kendra Allton, Kadir C Akdemir, Lalit R Patel, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C Barton
Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome-wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912096/drugging-acat1-for-cancer-therapy
#15
Javier Garcia-Bermudez, Kivanç Birsoy
In this issue, Fan et al. (2016) show that oncogenic tyrosine kinases can promote glycolysis by phosphorylating and stabilizing the tetrameric form of mitochondrial acetyl-coA acetyltransferase 1 (ACAT1). The authors further identify a small molecule ACAT1 inhibitor that displays anti-cancer effects.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912095/the-ras-mapk-axis-gets-stressed-out
#16
Scott A Foster, Shiva Malek
In this issue of Molecular Cell, Ritt et al. (2016) describe a stress-induced checkpoint that effectively suppresses RAS-MAPK signaling. This pathway, activated by agents such as Rigosertib that induce mitotic and oxidative stress, results in JNK-mediated inhibition of RAS-MAPK pathway components SOS and RAF.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912094/mre11-is-essential-for-the-removal-of-lethal-topoisomerase-2-covalent-cleavage-complexes
#17
Nguyen Ngoc Hoa, Tsubasa Shimizu, Zhong Wei Zhou, Zhao-Qi Wang, Rajashree A Deshpande, Tanya T Paull, Salma Akter, Masataka Tsuda, Ryohei Furuta, Ken Tsutsui, Shunichi Takeda, Hiroyuki Sasanuma
No abstract text is available yet for this article.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912093/direct-regulation-of-alternative-splicing-by-smad3-through-pcbp1-is-essential-to-the-tumor-promoting-role-of-tgf-%C3%AE
#18
Veenu Tripathi, Katherine M Sixt, Shaojian Gao, Xuan Xu, Jing Huang, Roberto Weigert, Ming Zhou, Ying E Zhang
No abstract text is available yet for this article.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912092/wrap53-a-natural-p53-antisense-transcript-required-for-p53-induction-upon-dna-damage
#19
Salah Mahmoudi, Sofia Henriksson, Martin Corcoran, Cristina Méndez-Vidal, Klas G Wiman, Marianne Farnebo
No abstract text is available yet for this article.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27889451/diet-microbiota-interactions-mediate-global-epigenetic-programming-in-multiple-host-tissues
#20
Kimberly A Krautkramer, Julia H Kreznar, Kymberleigh A Romano, Eugenio I Vivas, Gregory A Barrett-Wilt, Mary E Rabaglia, Mark P Keller, Alan D Attie, Federico E Rey, John M Denu
Histone-modifying enzymes regulate transcription and are sensitive to availability of endogenous small-molecule metabolites, allowing chromatin to respond to changes in environment. The gut microbiota produces a myriad of metabolites that affect host physiology and susceptibility to disease; however, the underlying molecular events remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues in a diet-dependent manner: consumption of a "Western-type" diet prevents many of the microbiota-dependent chromatin changes that occur in a polysaccharide-rich diet...
December 1, 2016: Molecular Cell
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