Feeding two birds with one scone: The dual roles of SMARCAL1 in antitumor immunity
In a recent issue of Cell, Leuzzi et  al.1 report the identification of the DNA translocase SMARCAL1 as a novel factor that dampens immune responses against tumor cells through two distinct mechanisms. (Source: Molecular Cell)
Source: Molecular Cell - March 7, 2024 Category: Cytology Authors: El éonore Toufektchan, John Maciejowski Tags: Spotlight Source Type: research

Deaminase deluge yields new opportunities for biotechnology and genome engineering
In this issue of Molecular Cell, Vaisvila et  al.1 report a tour de force functional characterization of a large and highly diverse set of polynucleotide cytosine deaminase (PCD) enzymes, which is already propelling new biotechnology applications. (Source: Molecular Cell)
Source: Molecular Cell - March 7, 2024 Category: Cytology Authors: Reuben S. Harris, Michael A. Carpenter Tags: Preview Source Type: research

Plot twists and cutting corners with atypical SMCs
In this issue of Molecular Cell, two papers provide insight into atypical structural maintenance of chromosomes protein complexes (SMCs). Jeppsson et  al.1 link Smc5/6 to supercoiled DNA, and Roisné-Hamelin et al.2 show how Wadjet SMC bends and cleaves invading DNAs. (Source: Molecular Cell)
Source: Molecular Cell - March 7, 2024 Category: Cytology Authors: Judith H.I. Haarhuis, Benjamin D. Rowland Tags: Preview Source Type: research

Meet the authors: Shouqiao Hou and Daichao Xu
Molecular Cell speaks with first author Shouqiao Hou and corresponding author Daichao Xu about the scientific journey toward their paper, “PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis” (in this issue of Molecular Cell), the challenges they faced, and interesting remaining questions for the field. (Source: Molecular Cell)
Source: Molecular Cell - March 7, 2024 Category: Cytology Authors: Shouqiao Hou, Daichao Xu Tags: Q & A Source Type: research

Dissection of a CTCF topological boundary uncovers principles of enhancer-oncogene regulation
Enhancer-gene communication is dependent on chromosome topology, which helps enhancers find their correct gene targets. Kim et  al. characterize topological boundaries that insulate the oncogenes FGF3 and FGF4 from a potent enhancer and show that combinatorial disruption of CTCF sites in the boundary results in enhancer-promoter contact and gene induction. (Source: Molecular Cell)
Source: Molecular Cell - March 6, 2024 Category: Cytology Authors: Kyung Lock Kim, Gilbert J. Rahme, Viraat Y. Goel, Chadi A. El Farran, Anders S. Hansen, Bradley E. Bernstein Tags: Short article Source Type: research

Sister chromatid cohesion halts DNA loop expansion
The cohesin ring has long been known for its role in mediating sister chromatids cohesion (SCC) in eukaryotes during G2/M. Basti é et al. demonstrate that these cohesins involved in SCC represent roadblocks to the extrusion of the chromatin loops that organize chromosomes at that stage in eukaryotes. (Source: Molecular Cell)
Source: Molecular Cell - March 6, 2024 Category: Cytology Authors: Nathalie Basti é, Christophe Chapard, Axel Cournac, Sanae Nejmi, Henri Mboumba, Olivier Gadal, Agnès Thierry, Frederic Beckouët, Romain Koszul Tags: Short article Source Type: research

Alternative splicing decouples local from global PRC2 activity
The mechanisms driving PRC2 subtype assembly and dimerization in  vivo are not yet understood. Arecco, Mocavini, et al. report an alternative splicing variant of SUZ12 (SUZ12-S) that promotes PRC2.1 dimerization, resulting in increased H3K27me3 deposition at target genes. SUZ12-S is necessary and sufficient for Polycomb gene repression in embryonic stem cells. (Source: Molecular Cell)
Source: Molecular Cell - March 6, 2024 Category: Cytology Authors: Niccol ò Arecco, Ivano Mocavini, Enrique Blanco, Cecilia Ballaré, Elina Libman, Sophie Bonnal, Manuel Irimia, Luciano Di Croce Tags: Article Source Type: research

Glycerophosphodiesters inhibit lysosomal phospholipid catabolism in Batten disease
Nyame et  al. reveal a pathological role for the Batten disease storage metabolites glycerophosphodiesters (GPDs) in the lysosome. GPDs bind and inhibit key lysosomal phospholipases, leading to accumulation of lysophospholipids, intermediates in phospholipid degradation known for their toxicity. Additionall y, they comprehensively characterize lysosomal phospholipid catabolism, a pathway crucial in several biological processes. (Source: Molecular Cell)
Source: Molecular Cell - March 5, 2024 Category: Cytology Authors: Kwamina Nyame, Andy Hims, Aya Aburous, Nouf N. Laqtom, Wentao Dong, Uche N. Medoh, Julia C. Heiby, Jian Xiong, Alessandro Ori, Monther Abu-Remaileh Tags: Article Source Type: research

Structural atlas of human primary microRNAs generated by SHAPE-MaP
Despite a crucial role in miRNA maturation, structural features of pri-miRNAs remain largely unclear. Using SHAPE-MaP, Baek et  al. determined highly reliable secondary structures of 476 human pri-miRNAs. Combined with processing data, the resource annotates the determinants of pri-miRNA processing with high accuracy and enables the designing of more potent shRNAs. (Source: Molecular Cell)
Source: Molecular Cell - March 5, 2024 Category: Cytology Authors: S. Chan Baek, Boseon Kim, Harim Jang, Kijun Kim, Il-Soo Park, Dal-Hee Min, V. Narry Kim Tags: Resource Source Type: research

Triaging of α-helical proteins to the mitochondrial outer membrane by distinct chaperone machinery based on substrate topology
Muthukumar et  al. use genome-wide and systematic arrayed CRISPRi screens to identify ⍺-helical OMM protein biogenesis and quality control factors that triage substrates by topology. They establish NAC as a targeting factor for polytopic proteins and identify TTC1 as a cytosolic chaperone for signal-anchored p roteins, using a C-terminal hydrophobic groove. (Source: Molecular Cell)
Source: Molecular Cell - February 29, 2024 Category: Cytology Authors: Gayathri Muthukumar, Taylor A. Stevens, Alison J. Inglis, Theodore K. Esantsi, Reuben A. Saunders, Fabian Schulte, Rebecca M. Voorhees, Alina Guna, Jonathan S. Weissman Tags: Article Source Type: research

Structure of the multi-subunit chloroplast RNA polymerase
do Prado et  al. report the cryo-EM structure of the plastid-encoded RNA polymerase complex from white mustard. The structure reveals the architecture of the major chloroplast transcription apparatus and provides insights into its unique associated factors. (Source: Molecular Cell)
Source: Molecular Cell - February 29, 2024 Category: Cytology Authors: Paula F.V. do Prado, Frederik M. Ahrens, Monique Liebers, Noah Ditz, Hans-Peter Braun, Thomas Pfannschmidt, Hauke S. Hillen Tags: Article Source Type: research

The proteomic landscape of genotoxic stress-induced micronuclei
Using subcellular fractionation followed by mass spectrometry-based proteomics, MacDonald et  al. profile the protein landscape of genotoxic stress-induced micronuclei (MN), compared with nuclei and cytoplasm. Components of the mRNA spliceosome were consistently deficient in MN, and the authors demonstrate that this elicits pathogenic MN DNA fragmentation in transcribing MN. (Source: Molecular Cell)
Source: Molecular Cell - February 28, 2024 Category: Cytology Authors: Kate M. MacDonald, Shahbaz Khan, Brian Lin, Rose Hurren, Aaron D. Schimmer, Thomas Kislinger, Shane M. Harding Tags: Resource Source Type: research

A di-acetyl-decorated chromatin signature couples liquid condensation to suppress DNA end synapsis
Bao et  al. reveal that the histone deacetylase complex MiDAC promotes H2AK5K9 deacetylation and licenses NHEJ synaptic complex assembly. In the context of MiDAC ablation, elevated H2AK5acK9ac serves as a docking signal for BRD4 to compartmentalize with KU around damaged chromatin, and this aberrant conde nsation inhibits DNA end synapsis and reduces genome stability. (Source: Molecular Cell)
Source: Molecular Cell - February 28, 2024 Category: Cytology Authors: Kaiwen Bao, Yanhui Ma, Yuan Li, Xilin Shen, Jiao Zhao, Shanshan Tian, Chunyong Zhang, Can Liang, Ziyan Zhao, Ying Yang, Kai Zhang, Na Yang, Fei-long Meng, Jihui Hao, Jie Yang, Tao Liu, Zhi Yao, Ding Ai, Lei Shi Tags: Article Source Type: research

Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation
Folded proteins cannot be degraded directly by the 26S proteasome and, therefore, require prior unfolding by the Cdc48 ATPase. Li et  al. use purified yeast components to reconstitute Cdc48-dependent protein degradation by the proteasome. They show that substrates are shuttled between the two molecular machines before being degraded. (Source: Molecular Cell)
Source: Molecular Cell - February 23, 2024 Category: Cytology Authors: Hao Li, Zhejian Ji, Joao A. Paulo, Steven P. Gygi, Tom A. Rapoport Tags: Article Source Type: research

Distinct negative elongation factor conformations regulate RNA polymerase II promoter-proximal pausing
This study provides the molecular basis for understanding how NELF-bound Pol II can be reactivated at paused or backtracked sites. (Source: Molecular Cell)
Source: Molecular Cell - February 23, 2024 Category: Cytology Authors: Bonnie G. Su, Seychelle M. Vos Tags: Article Source Type: research