ELAV and FNE Determine Neuronal Transcript Signatures through EXon-Activated Rescue
Carrasco et  al. show that the two neuron-specific RNA-binding proteins ELAV and FNE define the unique identity of neuronal messenger RNAs. When not repressed by ELAV, FNE undergoes a functional switch and rescues neuronal 3′ end processing and splicing in a process termed exon-activated functional rescue. (Source: Molecular Cell)
Source: Molecular Cell - September 30, 2020 Category: Cytology Authors: Judit Carrasco, Michael Rauer, Barbara Hummel, Dominika Grzejda, Carlos Alfonso-Gonzalez, Yeon Lee, Qingqing Wang, Monika Puchalska, Gerhard Mittler, Val érie Hilgers Tags: Short Article Source Type: research

Overlapping Activities of ELAV/Hu Family RNA Binding Proteins Specify the Extended Neuronal 3 ′ UTR Landscape in Drosophila
Neurons express much longer 3 ′ UTRs than other cell types. Here, Wei and Lee et al. determine that overlapping roles of Drosophila ELAV/Hu RNA binding proteins are necessary and sufficient to determine the extended 3′ UTR landscape. Moreover, their compensatory functions involve splicing and subcellular regulation between ELAV/Hu members. (Source: Molecular Cell)
Source: Molecular Cell - September 30, 2020 Category: Cytology Authors: Lu Wei, Seungjae Lee, Sonali Majumdar, Binglong Zhang, Piero Sanfilippo, Brian Joseph, Pedro Miura, Matthias Soller, Eric C. Lai Tags: Article Source Type: research

Structural Insights into the Roles of Metazoan-Specific Splicing Factors in the Human Step 1 Spliceosome
Bertram et  al. generate a cryo-EM structure of the human spliceosomal C complex at 3.4 Å core resolution. This structure provides new insights into the spliceosome’s molecular architecture between steps 1 and 2 of splicing, and the role of proteins in the formation of spliceosome’s catalytically active RNP conformation. (Source: Molecular Cell)
Source: Molecular Cell - September 30, 2020 Category: Cytology Authors: Karl Bertram, Leyla El Ayoubi, Olexandr Dybkov, Dmitry E. Agafonov, Cindy L. Will, Klaus Hartmuth, Henning Urlaub, Berthold Kastner, Holger Stark, Reinhard L ührmann Tags: Article Source Type: research

Hold on Tight: Lagging-Strand DNA Polymerases Synthesize Multiple Okazaki Fragments without Letting Go
Kapadia et  al. (2020) use an innovative single-molecule imaging approach in yeast cells to measure chromatin association of individual replisome subunits, thereby challenging the notion that lagging-strand DNA polymerases frequently dissociate from replisomes during DNA replication in vivo. (Source: Molecular Cell)
Source: Molecular Cell - September 30, 2020 Category: Cytology Authors: Vanessa Kellner, Duncan J. Smith Tags: Preview Source Type: research

Transmitting the Signal: Structure of the β1-Adrenergic Receptor-Gs Protein Complex
In this issue of Molecular Cell, Su et  al. (2020) report a cryo-EM structure of the β1-adrenergic receptor (β1AR) in complex with a heterotrimeric Gs protein, which offers novel insights into receptor activation and provides a structural framework to better understand the transducer-coupling mechanism for adrenergic receptors. (Source: Molecular Cell)
Source: Molecular Cell - September 30, 2020 Category: Cytology Authors: Shubhi Pandey, Shirsha Saha, Arun K. Shukla Tags: Preview Source Type: research

How Does the Alarmone ppGpp Change Bacterial Cell Metabolism? From Genome-wide Approaches to Structure to Physiology
Wang et  al. (2020) show that binding of the second messenger ppGpp to inosine-guanosine kinase (Gsk) in E. coli modulates the levels of the key metabolite phosphoribosyl pyrophosphate (pRpp), decreasing purine synthesis to favor amino acid synthesis during stress adaptation. (Source: Molecular Cell)
Source: Molecular Cell - September 30, 2020 Category: Cytology Authors: Anushya Petchiappan, Susan Gottesman Tags: Preview Source Type: research

A High-Throughput Screen for Transcription Activation Domains Reveals Their Sequence Features and Permits Prediction by Deep Learning
(Molecular Cell 78, 890 –902.e1–e6; June 4, 2020) (Source: Molecular Cell)
Source: Molecular Cell - September 16, 2020 Category: Cytology Authors: Ariel Erijman, Lukasz Kozlowski, Salma Sohrabi-Jahromi, James Fishburn, Linda Warfield, Jacob Schreiber, William S. Noble, Johannes S ӧding, Steven Hahn Tags: Correction Source Type: research

Gut Microbes ’ Impact on Oncogenic Drivers: Location Matters
Recent work by Kadosh et  al. (2020) suggests that mutant p53 activity in gut epithelia is influenced by local production of microbial metabolites. The switch of p53 from tumor suppressor to oncogene is location-dependent and is impacted by microbially derived gallic acid. (Source: Molecular Cell)
Source: Molecular Cell - September 16, 2020 Category: Cytology Authors: Michael G. White, Jennifer A. Wargo Tags: Spotlight Source Type: research

Osmotic Stress Triggers Phase Separation
In this issue of Molecular Cell, Jalihal et  al. (2020) show that cell volume changes upon osmotic stress result in rapid and reversible condensation of numerous multivalent proteins. (Source: Molecular Cell)
Source: Molecular Cell - September 16, 2020 Category: Cytology Authors: Sumit Majumder, Ankur Jain Tags: Preview Source Type: research

PARP-1 Flips the Epigenetic Switch on Obesity
PARP enzymes are increasingly taking on important roles beyond DNA repair. Huang et  al. (2020b) report how the NAD+-dependent ADP-ribosylation of histone H2B by PARP-1 in complex with a metabolic enzyme suppress the phosphorylation of an adjacent residue, impacting adipogenesis. (Source: Molecular Cell)
Source: Molecular Cell - September 16, 2020 Category: Cytology Authors: Carla E. Margulies, Andreas G. Ladurner Tags: Preview Source Type: research

Paolo Sassone-Corsi (1956 –2020)
The untimely death of Paolo Sassone-Corsi at the age of 64 on July 22nd has left both science and humanity diminished. Best known in recent years for his work on circadian rhythms, “Stop all the clocks,” the opening words of W.H. Auden’s “Funeral Blues,” have never seemed more appropriate. (Source: Molecular Cell)
Source: Molecular Cell - September 16, 2020 Category: Cytology Authors: Selma Masri, Colin R. Goding, Todd Leff Tags: Obituary Source Type: research

Histone Deacetylase 3 Couples Mitochondria to Drive IL-1 β-Dependent Inflammation by Configuring Fatty Acid Oxidation
Mitochondrial adaptations have been intimately linked to acute and chronic inflammation, but the metabolic cues and precise mechanisms remain unclear. Chi et  al. show that HDAC3 translocates to mitochondria to deacetylate the FAO enzyme HADHA for optimal NLRP3 inflammasome activation. (Source: Molecular Cell)
Source: Molecular Cell - September 14, 2020 Category: Cytology Authors: Zhexu Chi, Sheng Chen, Ting Xu, Wenxuan Zhen, Weiwei Yu, Danlu Jiang, Xingchen Guo, Zhen Wang, Kailian Zhang, Mobai Li, Jian Zhang, Hui Fang, Dehang Yang, Qizhen Ye, Xuyan Yang, Hui Lin, Fan Yang, Xue Zhang, Di Wang Tags: Article Source Type: research

Cell-Autonomous versus Systemic Akt Isoform Deletions Uncovered New Roles for Akt1 and Akt2 in Breast Cancer
Chen et  al. find that inducible systemic Akt1 deletion after tumor detection inhibits breast cancer metastasis of Akt-proficient tumor by inhibiting tumor-associated neutrophils. Inducible systemic Akt2 deletion does not inhibit breast cancer tumorigenesis and metastasis. Thus, specific Akt1 inhibition co uld be therapeutic for breast cancer metastasis regardless of tumor origin. (Source: Molecular Cell)
Source: Molecular Cell - September 13, 2020 Category: Cytology Authors: Xinyu Chen, Majd M. Ariss, Gopalakrishnan Ramakrishnan, Veronique Nogueira, Catherine Blaha, William Putzbach, Abul B.M.M.K. Islam, Maxim V. Frolov, Nissim Hay Tags: Article Source Type: research

Processive Activity of Replicative DNA Polymerases in the Replisome of Live Eukaryotic Cells
By establishing single-molecule methods in live budding yeast, Kapadia et  al. measured the binding kinetics in the eukaryotic replisome. They show that the leading and lagging strand polymerases, Pol δ and Pol ε, are stably bound to the replisome. In contrast, Pol α primase performs few priming cycles before dissociating. (Source: Molecular Cell)
Source: Molecular Cell - September 9, 2020 Category: Cytology Authors: Nitin Kapadia, Ziad W. El-Hajj, Huan Zheng, Thomas R. Beattie, Angela Yu, Rodrigo Reyes-Lamothe Tags: Article Source Type: research

Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex
McDowell et  al. describe structures of the GET insertase bound to the Get3 cytoplasmic chaperone. They reveal that membrane insertion of tail-anchored proteins by Get1/Get2 homologs requires the concerted action of a lipid-stabilized heterotetramer, a conserved cytoplasmic helix α3′, and a membrane-embedde d hydrophilic groove. (Source: Molecular Cell)
Source: Molecular Cell - September 8, 2020 Category: Cytology Authors: Melanie A. McDowell, Michael Heimes, Francesco Fiorentino, Shahid Mehmood, Ákos Farkas, Javier Coy-Vergara, Di Wu, Jani Reddy Bolla, Volker Schmid, Roger Heinze, Klemens Wild, Dirk Flemming, Stefan Pfeffer, Blanche Schwappach, Carol V. Robinson, Irmgard Tags: Article Source Type: research

Mitochondrial DNA Base Editing: Good Editing Things Still Come in Small Packages
The collaborative work of two HHMI groups, one at the University of Washington and the other at the Broad Institute of MIT and Harvard, led to the development of a novel molecular tool to edit single bases in the mtDNA (Mok et  al., 2020). (Source: Molecular Cell)
Source: Molecular Cell - September 2, 2020 Category: Cytology Authors: Sandra R. Bacman, Carlos T. Moraes Tags: Spotlight Source Type: research

Resveratrol: Friend or Foe?
In this issue of Molecular Cell, Benslimane et  al. (2020) perform a CRISPR-Cas9 chemogenomic screen, identifying a network of DNA replication and genome integrity genes with the nutraceutical compound Resveratrol and its analog Pterostilbene, linking these compounds to the induction of DNA replication stress in mammalian cells. (Source: Molecular Cell)
Source: Molecular Cell - September 2, 2020 Category: Cytology Authors: Thomas L. Clarke, Raul Mostoslavsky Tags: Preview Source Type: research

Your Base Editor Might Be Flirting with Single (Stranded) DNA: Faithful On-Target CRISPR Base Editing without Promiscuous Deamination
Jin et  al. (2020) engineered new variants of CRISPR base editors that make precise genomic edits in rice protoplasts while minimizing untargeted mutagenesis. (Source: Molecular Cell)
Source: Molecular Cell - September 2, 2020 Category: Cytology Authors: Scott P. Collins, Chase L. Beisel Tags: Preview Source Type: research

Genetic Characterization of Three Distinct Mechanisms Supporting RNA-Driven DNA Repair and Modification Reveals Major Role of DNA Polymerase ζ
Still much is unknown about the roles of RNA in DNA repair and modification. Meers et  al. characterize three genetic mechanisms by which RNA can directly or indirectly transfer genetic information to DNA in yeast cells and uncover that direct RNA-templated DNA recombination is aided by translesion DNA polymerase ζ. (Source: Molecular Cell)
Source: Molecular Cell - September 1, 2020 Category: Cytology Authors: Chance Meers, Havva Keskin, Gabor Banyai, Olga Mazina, Taehwan Yang, Alli L. Gombolay, Kuntal Mukherjee, Efiyenia I. Kaparos, Gary Newnam, Alexander Mazin, Francesca Storici Tags: Article Source Type: research

Molecular Connectivity of Mitochondrial Gene Expression and OXPHOS Biogenesis
Singh et  al. delineate proximity interactomes of proteins implicated in various steps of mitochondrial gene expression. The highly specific network reveals that strategically important ribosomal sites are populated by factors mediating distinct processes. For instance, the mitoribosomal polypeptide tunnel exit orchestrates membrane insertion, redox co-factor acquisition, and early OXPHOS assembly. (Source: Molecular Cell)
Source: Molecular Cell - August 31, 2020 Category: Cytology Authors: Abeer Prakash Singh, Roger Salvatori, Wasim Aftab, Andreas Aufschnaiter, Andreas Carlstr öm, Ignasi Forne, Axel Imhof, Martin Ott Tags: Article Source Type: research

Structure-Based Mechanisms of a Molecular RNA Polymerase/Chaperone Machine Required for Ribosome Biosynthesis
Huang et  al. structurally and functionally analyzed ribosomal RNA-transcription-elongation complexes, showing how transcription factors and RNA elements are organized on RNA polymerase to suppress pausing and pre-mature termination and how the factors form a composite RNA chaperone that supports co-transcr iptional RNA folding and annealing of distal RNA regions. (Source: Molecular Cell)
Source: Molecular Cell - August 30, 2020 Category: Cytology Authors: Yong-Heng Huang, Tarek Hilal, Bernhard Loll, J örg Bürger, Thorsten Mielke, Christoph Böttcher, Nelly Said, Markus C. Wahl Tags: Article Source Type: research

DNA Damage Promotes TMPRSS2-ERG Oncoprotein Destruction and Prostate Cancer Suppression via Signaling Converged by GSK3 β and WEE1
TMPRSS2-ERG oncoprotein plays a pivotal role in prostate oncogenesis and progression and is a potential therapeutic target of prostate cancer. Hong et  al. reveal a previously unrecognized TMPRSS2-ERG protein destruction mechanism, and intact PTEN and GSK3β signaling are essential for effective targeting of TMPRSS2-ERG by genotoxic therapeutics in prostate cancer. (Source: Molecular Cell)
Source: Molecular Cell - August 30, 2020 Category: Cytology Authors: Zhe Hong, Wei Zhang, Donglin Ding, Zhenlin Huang, Yuqian Yan, William Cao, Yunqian Pan, Xiaonan Hou, Saravut J. Weroha, R. Jeffrey Karnes, Dejie Wang, Qiang Wu, Denglong Wu, Haojie Huang Tags: Article Source Type: research

Phase Separation in Cell Division
The process of cell division requires spatial and temporal control over microtubule-associated proteins and their regulatory factors to promote the assembly and function of the microtubule spindle. In this review, Ong and Torres describe the role of phase separation in cell division and in coordinating and organizing the assembly of cell division factors and the microtubule spindle. (Source: Molecular Cell)
Source: Molecular Cell - August 27, 2020 Category: Cytology Authors: Joseph Y. Ong, Jorge Z. Torres Tags: Review Source Type: research

ppGpp Coordinates Nucleotide and Amino-Acid Synthesis in E. coli During Starvation
Wang et  al. demonstrate that ppGpp, the universally conserved growth regulator in bacteria, directly inhibits the purine nucleotide salvage enzyme Gsk. By characterizing a Gsk variant that is insensitive to ppGpp, they demonstrate that inhibiting purine nucleotide synthesis is required during starvation t o maintain levels of the metabolite pRpp, which is required for synthesizing histidine and tryptophan. (Source: Molecular Cell)
Source: Molecular Cell - August 26, 2020 Category: Cytology Authors: Boyuan Wang, Robert A. Grant, Michael T. Laub Tags: Article Source Type: research

Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change
Cells constantly experience osmotic variation. These external changes lead to changes in cell volume and, consequently, the internal state of molecular crowding. Jalihal and Pitchiaya et  al. show that multimeric proteins respond rapidly to such cellular changes by undergoing fast and reversible phase separation. (Source: Molecular Cell)
Source: Molecular Cell - August 26, 2020 Category: Cytology Authors: Ameya P. Jalihal, Sethuramasundaram Pitchiaya, Lanbo Xiao, Pushpinder Bawa, Xia Jiang, Karan Bedi, Abhijit Parolia, Marcin Cieslik, Mats Ljungman, Arul M. Chinnaiyan, Nils G. Walter Tags: Article Source Type: research

DNA Structure-Specific Cleavage of DNA-Protein Crosslinks by the SPRTN Protease
Reinking et  al. show that the protease SPRTN degrades DNA-protein crosslinks in a DNA structure-specific manner, which restricts cleavage to biologically relevant scenarios. NMR analysis reveals that specificity is achieved by a bipartite strategy relying on two DNA binding interfaces that recognize single- a nd double-stranded features within the substrate. (Source: Molecular Cell)
Source: Molecular Cell - August 25, 2020 Category: Cytology Authors: Hannah K. Reinking, Hyun-Seo Kang, Maximilian J. G ötz, Hao-Yi Li, Anja Kieser, Shubo Zhao, Aleida C. Acampora, Pedro Weickert, Evelyn Fessler, Lucas T. Jae, Michael Sattler, Julian Stingele Tags: Article Source Type: research

Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis
Huang et  al. show that the nuclear NAD+ synthase, NMNAT-1, directs PARP-1 catalytic activity to Glu and Asp residues on histones. Physiological ADP-ribosylation of histone H2B-Glu35 by snoRNA-activated PARP-1 with NMNAT-1 inhibits AMPK-mediated phosphorylation of adjacent H2B-Ser36, which is required for p roadipogenic gene expression and fat metabolism in vivo. (Source: Molecular Cell)
Source: Molecular Cell - August 19, 2020 Category: Cytology Authors: Dan Huang, Cristel V. Camacho, Rohit Setlem, Keun Woo Ryu, Balaji Parameswaran, Rana K. Gupta, W. Lee Kraus Tags: Article Source Type: research

Inositol Pyrophosphates Mediate the DNA-PK/ATM-p53 Cell Death Pathway by Regulating CK2 Phosphorylation of Tti1/Tel2
(Molecular Cell 54, 119 –132; April 10, 2014) (Source: Molecular Cell)
Source: Molecular Cell - August 19, 2020 Category: Cytology Authors: Feng Rao, Jiyoung Cha, Jing Xu, Risheng Xu, M. Scott Vandiver, Richa Tyagi, Robert Tokhunts, Michael A. Koldobskiy, Chenglai Fu, Roxanne Barrow, Mingxuan Wu, Dorothea Fiedler, James C. Barrow, Solomon H. Snyder Tags: Correction Source Type: research

Partitioning of Chemotherapeutics into Nuclear Condensates —Opening the Door to New Approaches for Drug Development
Klein et  al. (2020) demonstrate for the first time that small-molecule cancer therapeutics are selectively partitioned and concentrated within phase-separated nuclear condensates, providing new insights to drug efficacy and creating the opportunity for enhanced control of therapeutic targeting. (Source: Molecular Cell)
Source: Molecular Cell - August 19, 2020 Category: Cytology Authors: Thomas P. Howard, Charles W.M. Roberts Tags: Spotlight Source Type: research

Two Ribosomes Are Better Than One... Sometimes
In this issue of Molecular Cell, Meydan and Guydosh present an elegant and rigorous addition to the exciting investigation of the roles played by ribosome collisions in eukaryotic translation and cellular homeostasis. (Source: Molecular Cell)
Source: Molecular Cell - August 19, 2020 Category: Cytology Authors: Alexandra N. Olson, Jonathan D. Dinman Tags: Preview Source Type: research

Should I Stay or Should I Go: eIF3 Remains Ribosome Associated and Is Required for Elongation
Wagner et  al. (2020), Bohlen et al. (2020), and Lin et al. (2020) use Sel-TCP-seq or selective ribosome profiling to gain insights into mRNA translation initiation, highlighting distinctions between yeast and higher eukaryotes and a role for eIF3 in elongation. (Source: Molecular Cell)
Source: Molecular Cell - August 19, 2020 Category: Cytology Authors: Tuija P öyry, Mark Stoneley, Anne E. Willis Tags: Preview Source Type: research

Beth Levine (1960 –2020)
Beth Levine, founder of modern mammalian autophagy, died on June 15, 2020. Her life ’s work, which bridged fundamental cellular biology and human disease, elucidated gene regulatory mechanisms of mammalian autophagy and implicated this pathway in the pathogenesis of a spectrum of diseases. Born on April 7, 1960 in Newark, New Jersey, Beth received an AB magna cum laude in French Studies from Brown University and an MD from Cornell University Medical College. She completed her internship and residency in Internal Medicine at Mount Sinai Hospital in New York City and her fellowship in Infectious Diseases at Johns Hopki...
Source: Molecular Cell - August 19, 2020 Category: Cytology Authors: Ramnik J. Xavier, Herbert W. Virgin Tags: Obituary Source Type: research

Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β1-Adrenergic Receptor
Su et  al. report the cryo-EM structure of the complex of isoproterenol-bound β1-adrenergic receptor and heterotrimeric Gs-protein. The structural and functional studies reveal insights into the activation of Gs by β1-adrenergic receptor. This work advances our understanding of the control of heart rat e and contractility by the nervous system and hormones. (Source: Molecular Cell)
Source: Molecular Cell - August 18, 2020 Category: Cytology Authors: Minfei Su, Lan Zhu, Yixiao Zhang, Navid Paknejad, Raja Dey, Jianyun Huang, Ming-Yue Lee, Dewight Williams, Kelsey D. Jordan, Edward T. Eng, Oliver P. Ernst, Joel R. Meyerson, Richard K. Hite, Thomas Walz, Wei Liu, Xin-Yun Huang Tags: Article Source Type: research

DNA Damage and Cancer Immunotherapy: A STING in the Tale
The DNA damage response and the immune response provide two distinct barriers to tumorigenesis. Reisl änder et al. provide a comprehensive yet concise overview of the molecular interplay between these two anti-tumoral mechanisms. They further discuss how combinations of DNA damage response and immune checkpoint inhibitors are exploited for cancer therapy. (Source: Molecular Cell)
Source: Molecular Cell - August 16, 2020 Category: Cytology Authors: Timo Reisl änder, Florian J. Groelly, Madalena Tarsounas Tags: Review Source Type: research

Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication
In this study, Klann et  al. dissected the host cell signaling landscape upon infection with SARS-CoV-2. Mapping differential signaling networks identified a number of pathways activated during infection. Drug-target network analysis revealed potential therapeutic targets. Growth factor receptor signaling was highly activ ated upon infection and its inhibition prevented SARS-CoV-2 replication in cells. (Source: Molecular Cell)
Source: Molecular Cell - August 9, 2020 Category: Cytology Authors: Kevin Klann, Denisa Bojkova, Georg Tascher, Sandra Ciesek, Christian M ünch, Jindrich Cinatl Tags: Resource Source Type: research

An In  Vitro Assembly System Identifies Roles for RNA Nucleation and ATP in Yeast Stress Granule Formation
Begovich and Wilhelm present a yeast stress granule reconstitution using cytoplasmic extract fraction and RNA stem loop arrays. Using this system, they identify how ATP levels, ATPase activity, and RNA condensate composition regulate stress granule formation. (Source: Molecular Cell)
Source: Molecular Cell - August 9, 2020 Category: Cytology Authors: Kyle Begovich, James E. Wilhelm Tags: Article Source Type: research

GIT/PIX Condensates Are Modular and Ideal for Distinct Compartmentalized Cell Signaling
Cells often concentrate limited amounts of enzymes at specific subcellular regions for distinct functions. Zhu et  al. show that the small GTPase regulatory enzymes GIT and PIX autonomously form phase-separated condensates without the need for scaffolding molecules. GIT/PIX condensates are modular and positioned at specific cellular compartments for distinct signaling. (Source: Molecular Cell)
Source: Molecular Cell - August 9, 2020 Category: Cytology Authors: Jinwei Zhu, Qingqing Zhou, Yitian Xia, Lin Lin, Jianchao Li, Mengjuan Peng, Rongguang Zhang, Mingjie Zhang Tags: Article Source Type: research

The 3D Topography of Mitotic Chromosomes
Split sister axes of mitotic chromosomes are linked by “mini-axis” bridges that provide mechanical stability. Existence of bridges precludes helical chromosome coiling. Instead, unsplit prophase linear loop/axis arrays, with deformed axes comprising sequential half-helical segments of alternating handedness (perversions), undergo lateral splitting a nd then compact via simple linear shortening. (Source: Molecular Cell)
Source: Molecular Cell - August 6, 2020 Category: Cytology Authors: Lingluo Chu, Zhangyi Liang, Maria Mukhina, Jay Fisher, Nadine Vincenten, Zheng Zhang, John Hutchinson, Denise Zickler, Nancy Kleckner Tags: Article Source Type: research

Advances in Chromatin and Chromosome Research: Perspectives from Multiple Fields
In this collaborative review, Agbleke et  al. discuss the development and application of new technologies to probe chromatin and chromosome biology questions. The authors examine new chromatin concepts, drawing on perspectives from researchers within the chromatin community as well as from those in adjacent fields. (Source: Molecular Cell)
Source: Molecular Cell - August 6, 2020 Category: Cytology Authors: Andrews Akwasi Agbleke, Assaf Amitai, Jason D. Buenrostro, Aditi Chakrabarti, Lingluo Chu, Anders S. Hansen, Kristen M. Koenig, Ajay S. Labade, Sirui Liu, Tadasu Nozaki, Sergey Ovchinnikov, Andrew Seeber, Haitham A. Shaban, Jan-Hendrik Spille, Andrew D. S Tags: Technology Review Source Type: research

Primary Role of the Nucleosome
The coiling of DNA in the core nucleosome inhibits the initiation of transcription. The core nucleosome thus serves as a general gene repressor and prevents pervasive intergenic and intragenic transcription. This fundamental regulatory role of the nucleosome apparently emerged before the acquisition of the histone tails. (Source: Molecular Cell)
Source: Molecular Cell - August 5, 2020 Category: Cytology Authors: Roger D. Kornberg, Yahli Lorch Tags: Perspective Source Type: research

Amplifying the Noise: Oncometabolites Mask an Epigenetic Signal of DNA Damage
A recent study (Sulkowski et  al., 2020) reveals that oncometabolites, which are produced by metabolic gene mutations in many cancers, sensitize cells to PARP inhibition by antagonizing histone demethylation and obscuring epigenetic marks that are necessary for efficient DNA repair. (Source: Molecular Cell)
Source: Molecular Cell - August 5, 2020 Category: Cytology Authors: Milan R. Savani, Kalil G. Abdullah, Samuel K. McBrayer Tags: Spotlight Source Type: research

Unwinding the Role of FACT in Cas9-based Genome Editing
In a recent issue of Molecular Cell, Wang et  al. (2020) employ unbiased proteomics approaches and live-cell imaging to reveal a key role for the histone chaperone complex FACT (SPT16 and SSRP1) in governing Cas9 turnover at the DNA target site during genome and epigenome editing. (Source: Molecular Cell)
Source: Molecular Cell - August 5, 2020 Category: Cytology Authors: Brian D. Cosgrove, Charles A. Gersbach Tags: Preview Source Type: research

TDP-43 Nuclear Bodies: A NEAT Response to Stress?
In this issue of Molecular Cell, Wang et  al. (2020) investigate stress-induced nuclear condensates of the RNA-binding protein TDP-43, uncovering a protective function for these granules as well as an RNA-dependent mechanism for scaffolding them. (Source: Molecular Cell)
Source: Molecular Cell - August 5, 2020 Category: Cytology Authors: Ahmed M. Malik, Sami J. Barmada Tags: Preview Source Type: research

Looping the (R) Loop in DSB Repair via RNA Methylation
In this issue of Molecular Cell, Zhang et  al. (2020) reveal that ATM triggers RNA methylation of DNA-RNA hybrids formed at double-strand breaks (DSBs) to modulate repair, adding a new layer of complexity to RNA’s role in the DNA damage response. (Source: Molecular Cell)
Source: Molecular Cell - August 5, 2020 Category: Cytology Authors: Bel én Gómez-González, Andrés Aguilera Tags: Preview Source Type: research

A Structure-Based Mechanism for DNA Entry into the Cohesin Ring
Cohesin is a ring-shaped protein complex that topologically entraps DNA to fulfil key functions in chromosome architecture. In a multidisciplinary approach, Higashi et  al. use cryo-EM and biochemical techniques to describe how ATP-fueled structural changes of the cohesin complex drive the DNA entry reaction into the cohesin ring. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2020 Category: Cytology Authors: Torahiko L. Higashi, Patrik Eickhoff, Joana S. Sousa, Julia Locke, Andrea Nans, Helen R. Flynn, Ambrosius P. Snijders, George Papageorgiou, Nicola O ’Reilly, Zhuo A. Chen, Francis J. O’Reilly, Juri Rappsilber, Alessandro Costa, Frank Uhlmann Tags: Article Source Type: research

Genome-Wide Screens Reveal that Resveratrol Induces Replicative Stress in Human Cells
Unbiased CRISPR genetic screens in human cells treated with the natural product resveratrol pinpointed DNA replication stress induction as a major anti-proliferative effect of resveratrol. This finding may have implications for the potential mechanisms of action of resveratrol in model organisms. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2020 Category: Cytology Authors: Yahya Benslimane, Thierry Bertomeu, Jasmin Coulombe-Huntington, Mary McQuaid, Mar ía Sánchez-Osuna, David Papadopoli, Daina Avizonis, Mariana De Sa Tavares Russo, Caroline Huard, Ivan Topisirovic, Hugo Wurtele, Mike Tyers, Lea Harrington Tags: Short Article Source Type: research

The Lon Protease Links Nucleotide Metabolism with Proteotoxic Stress
Competition between misfolded and natively folded substrates for a limited pool of the highly conserved Lon protease governs stress adaptation. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2020 Category: Cytology Authors: Rilee D. Zeinert, Hamid Baniasadi, Benjamin P. Tu, Peter Chien Tags: Article Source Type: research

Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting
Robson et  al. examine the molecular basis of the coronavirus proofreading mechanism and how this contributes to the resistance of this family of viruses to nucleoside analog (NA) antiviral drugs. They discuss antisense oligonucleotide (ASO) therapy in combination with NAs to potentially improve the potency and delivery of antiviral drugs. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2020 Category: Cytology Authors: Fran Robson, Khadija Shahed Khan, Thi Khanh Le, Cl ément Paris, Sinem Demirbag, Peter Barfuss, Palma Rocchi, Wai-Lung Ng Tags: Review Source Type: research

The Dynamics of Transcriptional Activation by Hepatic Reprogramming Factors
During the direct reprogramming of fibroblasts to hepatocyte-like cells, Foxa3 acts as a pioneer factor, similar to Foxa1 and Foxa2, but leaves its binding site to interact and migrate with RNA polymerase II, thereby inducing the transcription of target genes. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2020 Category: Cytology Authors: Kenichi Horisawa, Miyako Udono, Kazuko Ueno, Yasuyuki Ohkawa, Masao Nagasaki, Sayaka Sekiya, Atsushi Suzuki Tags: Article Source Type: research

XACT-Seq Comprehensively Defines the Promoter-Position and Promoter-Sequence Determinants for Initial-Transcription Pausing
Winkelman et  al. report a protein-DNA photocrosslinking method that provides single-nucleotide-resolution readout of RNA polymerase active-center position relative to DNA and enables analysis of initial-transcription pausing. Analysis of 411 (∼4,000,000) promoter sequences defines positional determinants and sequence determinants for initial-transcription pausing by bacterial RNA polymerase in vitro and in vivo. (Source: Molecular Cell)
Source: Molecular Cell - August 2, 2020 Category: Cytology Authors: Jared T. Winkelman, Chirangini Pukhrambam, Irina O. Vvedenskaya, Yuanchao Zhang, Deanne M. Taylor, Premal Shah, Richard H. Ebright, Bryce E. Nickels Tags: Article Source Type: research