PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis
Hou et al. demonstrate that upon activation of necroptosis and recruitment by TAX1BP1, PARP5A and RNF146 undergo phase separation to perform PARylation-dependent ubiquitination (PARdU) of RIPK1. PARdU occurs on the K376 residue of mouse RIPK1, which promotes proteasomal degradation of kinase-activated RI PK1 to put necroptosis in check. (Source: Molecular Cell)
Source: Molecular Cell - January 24, 2024 Category: Cytology Authors: Shouqiao Hou, Jian Zhang, Xiaoyan Jiang, Yuanxin Yang, Bing Shan, Mengmeng Zhang, Cong Liu, Junying Yuan, Daichao Xu Tags: Article Source Type: research
Serine synthesis sustains macrophage IL-1 β production via NAD+-dependent protein acetylation
Wang et al. reveal that de novo serine synthesis mediates inflammatory responses by orchestrating IL-1β production via PHGDH-mediated NAD+ accumulation, which limits SIRT1 and SIRT3 expression and activation. Subsequently, sustained TLR4 transcriptional activation through H3K9/27 acetylation and acetylat ion-mediated NLRP3 activation supports IL-1β expression and maturation. (Source: Molecular Cell)
Source: Molecular Cell - January 23, 2024 Category: Cytology Authors: Chuanlong Wang, Qingyi Chen, Siyuan Chen, Lijuan Fan, Zhending Gan, Muyang Zhao, Lexuan Shi, Peng Bin, Guan Yang, Xihong Zhou, Wenkai Ren Tags: Article Source Type: research
HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III
Leone and Srivastava et al. describe the direct interaction of chaperone proteins with RNA in human cells. They describe the localization of HSP70 on genes transcribed by RNA polymerase III. HSP70 interacts with the transcribed tRNA, and this interaction alleviates the inhibitory effect of cognate tRNA transcript on tRNA gene transcription. (Source: Molecular Cell)
Source: Molecular Cell - January 23, 2024 Category: Cytology Authors: Sergio Leone, Avinash Srivastava, Andr és Herrero-Ruiz, Barbara Hummel, Lena Tittel, Roberto Campalastri, Fernando Aprile-Garcia, Jun Hao Tan, Prashant Rawat, Patrik Andersson, Anne E. Willis, Ritwick Sawarkar Tags: Article Source Type: research
EXO1 protects BRCA1-deficient cells against toxic DNA lesions
van de Kooij et al. identify loss of the exonuclease EXO1 as a vulnerability of BRCA1-deficient cells. Mechanistically, cells deficient for both BRCA1 and EXO1 suffer from unrepaired DNA double-stranded breaks due to the loss of two break repair pathways, homologous recombination, and single-strand annealing. (Source: Molecular Cell)
Source: Molecular Cell - January 23, 2024 Category: Cytology Authors: Bert van de Kooij, Anne Schreuder, Raphael Pavani, Veronica Garzero, Sidrit Uruci, Tiemen J. Wendel, Arne van Hoeck, Marta San Martin Alonso, Marieke Everts, Dana Koerse, Elsa Callen, Jasper Boom, Hailiang Mei, Edwin Cuppen, Martijn S. Luijsterburg, Marce Tags: Article Source Type: research
BLM and BRCA1-BARD1 coordinate complementary mechanisms of joint DNA molecule resolution
Tsukada et al. identify a negative genetic interaction between the BLM helicase and the BRCA1-BARD1 complex. They reveal that this is due to a previously overlooked role for BARD1 in recruiting the SLX4 structure-specific nuclease complex to resolve DNA intermediates and joint molecules left unprocessed by B LM prior to cell division. (Source: Molecular Cell)
Source: Molecular Cell - January 23, 2024 Category: Cytology Authors: Kaima Tsukada, Samuel E. Jones, Julius Bannister, Mary-Anne Durin, Iolanda Vendrell, Matthew Fawkes, Roman Fischer, Benedikt M. Kessler, J. Ross Chapman, Andrew N. Blackford Tags: Article Source Type: research
Regulation of replicative histone RNA metabolism by the histone chaperone ASF1
Mendiratta et al. explore whether and how histone chaperones control histone supply in human cells to coordinate chromatin assembly with DNA replication during S phase. They reveal that the H3-H4 histone chaperone ASF1 specifically regulates the 3′ end processing of replicative histone RNAs to fine-tune the r eplicative histone dosage. (Source: Molecular Cell)
Source: Molecular Cell - January 22, 2024 Category: Cytology Authors: Shweta Mendiratta, Dominique Ray-Gallet, S ébastien Lemaire, Alberto Gatto, Audrey Forest, Maciej A. Kerlin, Geneviève Almouzni Tags: Short article Source Type: research
SATB2 organizes the 3D genome architecture of cognition in cortical neurons
Wahl et al. establish SATB2 as a cell-type-specific 3D genome modulator in cortical neurons. It acts independently or in cooperation with CTCF to modify the 3D genome architecture. SATB2 specifically affects genetic loci involved in synaptic function, cognition, learning, and memory. (Source: Molecular Cell)
Source: Molecular Cell - January 19, 2024 Category: Cytology Authors: Nico Wahl, Sergio Espeso-Gil, Paola Chietera, Amelie Nagel, Aod án Laighneach, Derek W. Morris, Prashanth Rajarajan, Schahram Akbarian, Georg Dechant, Galina Apostolova Tags: Article Source Type: research
N6-methyladenosine in 5 ′ UTR does not promote translation initiation
Guca et al. use an integrative approach, including functional, structural, single-molecule, and computational approaches, and show that a single m6A in the 5′ UTR does not affect translation dynamics under homeostatic conditions or stress. They observe interactions between m6A with an arginine side chai n of eIF2α, although with only a marginal energy contribution. (Source: Molecular Cell)
Source: Molecular Cell - January 19, 2024 Category: Cytology Authors: Ewelina Guca, Rodrigo Alarcon, Michael Z. Palo, Leonardo Santos, Santiago Alonso-Gil, Marcos Davyt, Leonardo H.F. de Lima, Fanny Boissier, Sarada Das, Bojan Zagrovic, Joseph D. Puglisi, Yaser Hashem, Zoya Ignatova Tags: Short article Source Type: research
BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair
Lim et al. report that replication gap suppression and fork protection require BRCA2 stabilization of RAD51 filaments but have minimal impact on genome integrity, oncogenesis, and drug resistance compared with homologous recombination deficiency. However, BRCA2 suppression of PRIMPOL-mediated gaps confer s resistance to hmdU, the incorporation of which leads to cytotoxic abasic sites. (Source: Molecular Cell)
Source: Molecular Cell - January 19, 2024 Category: Cytology Authors: Pei Xin Lim, Mahdia Zaman, Weiran Feng, Maria Jasin Tags: Article Source Type: research
Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide
Russo, Gualdrini et al. report a direct association of the Mediator complex with nuclear 2-ketoacid dehydrogenases such as pyruvate dehydrogenase (PDH), resulting in the local production of acetyl-CoA and the boosting of histone acetylation. The inhibition of Mediator-bound PDH by NO in LPS-activated macrophages impa ired de novo histone acetylation. (Source: Molecular Cell)
Source: Molecular Cell - January 18, 2024 Category: Cytology Authors: Marta Russo, Francesco Gualdrini, Veronica Vallelonga, Elena Prosperini, Roberta Noberini, Silvia Pedretti, Carolina Borriero, Pierluigi Di Chiaro, Sara Polletti, Gabriele Imperato, Mattia Marenda, Chiara Ghirardi, Fabio Bedin, Alessandro Cuomo, Simona Ro Tags: Short article Source Type: research
Mechanisms of RNF168 nucleosome recognition and ubiquitylation
RNF168 controls the chromatin recruitment of several DNA damage response (DDR) proteins, but its mechanisms of action remain unclear. Hu et al. unveil how RNF168 selectively ubiquitylates histone H2A in the nucleosome and reads its own ubiquitylation products, allowing for propagation on chromatin of ubiquitin marks recognized by DDR proteins. (Source: Molecular Cell)
Source: Molecular Cell - January 18, 2024 Category: Cytology Authors: Qi Hu, Debiao Zhao, Gaofeng Cui, Janarjan Bhandari, James R. Thompson, Maria Victoria Botuyan, Georges Mer Tags: Article Source Type: research
Exploiting activation and inactivation mechanisms in type I-C CRISPR-Cas3 for genome-editing applications
Hu et al. elucidate the PAM recognition, R-loop formation, and Cas3 recruitment processes for type I-C CRISPR activation. Two anti-CRISPR proteins, AcrIC8 and AcrIC9, block PAM recognition by I-C Cascade via distinct mechanisms and can serve as off-switches for type I-C genome deletion and transcription al activation applications in human cells. (Source: Molecular Cell)
Source: Molecular Cell - January 18, 2024 Category: Cytology Authors: Chunyi Hu, Mason T. Myers, Xufei Zhou, Zhonggang Hou, Macy L. Lozen, Ki Hyun Nam, Yan Zhang, Ailong Ke Tags: Article Source Type: research
Epigenetic regulatory layers in the 3D nucleus
Genomes are folded into three-dimensional structures that serve as substrates for the actions of proteins and RNAs in gene regulation. Here, we give an overview of the many gene regulatory mechanisms that co-exist in living cells and elaborate on future approaches to deepen our understanding of their interplay in genome function. (Source: Molecular Cell)
Source: Molecular Cell - January 18, 2024 Category: Cytology Authors: Andr éa Willemin, Dominik Szabó, Ana Pombo Tags: Perspective Source Type: research
Enzymatic and non-enzymatic transnitrosylation: “SCAN”ning the SNO-proteome
In a recent study in Cell, Zhou et al.1 propose enzymatic transfer of nitric-oxide (NO)-related species from SNO-CoA to target proteins involved in insulin signaling; this function comprises an SNO-CoA-Assisted Nitrosylase (SCAN). (Source: Molecular Cell)
Source: Molecular Cell - January 18, 2024 Category: Cytology Authors: Tomohiro Nakamura, Stuart A. Lipton Tags: Spotlight Source Type: research
Actions speak louder than ORFs: A non-canonical microprotein promotes medulloblastoma oncogenesis
In this issue of Molecular Cell, Hofman et al.1 identify the translation of a non-canonical upstream open reading frame of the ASNSD1 gene into a microprotein that supports medulloblastoma growth. (Source: Molecular Cell)
Source: Molecular Cell - January 18, 2024 Category: Cytology Authors: Alberto Delaidelli, Jessica Oliveira de Santis, Poul H. Sorensen Tags: Preview Source Type: research
