FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress
The Fanconi anemia pathway alleviates oncogene-induced replication stress. Brunner et al. report that the ubiquitin ligase SCFFBXL12 targets the key Fanconi anemia protein FANCD2 for proteasomal degradation. They demonstrate that this occurs in the vicinity of replication forks and is critical for replication recovery and survival under CDK-driven replication stress. (Source: Molecular Cell)
Source: Molecular Cell - August 16, 2023 Category: Cytology Authors: Andr ä Brunner, Qiuzhen Li, Samuele Fisicaro, Alexandros Kourtesakis, Johanna Viiliäinen, Henrik J. Johansson, Vijaya Pandey, Adarsh K. Mayank, Janne Lehtiö, James A. Wohlschlegel, Charles Spruck, Juha K. Rantala, Lukas M. Orre, Olle Sangfelt Tags: Article Source Type: research
Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms
Nagasaka et al. discover that cohesin’s sister chromatid cohesion and DNA loop extrusion functions can be partially separated. Their observations support the notion that cohesion establishment and the accumulation of cohesin at CTCF boundaries both depend on entrapment of DNA inside the cohesin ring via ope ning of cohesin’s hinge domain. (Source: Molecular Cell)
Source: Molecular Cell - August 16, 2023 Category: Cytology Authors: Kota Nagasaka, Iain F. Davidson, Roman R. Stocsits, Wen Tang, Gordana Wutz, Paul Batty, Melanie Panarotto, Gabriele Litos, Alexander Schleiffer, Daniel W. Gerlich, Jan-Michael Peters Tags: Article Source Type: research
A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms
Phosphorylation activates P38 MAPK in response to many stimuli. Cao et al. reveal two mechanisms by which a peroxiredoxin transmits H2O2 signals to P38: (1) forming a Prdx-P38 complex that provides a scaffold for non-canonical activation of P38 MAPKK and (2) alleviating inhibition by a redox-sensitive P38 phosphatase. (Source: Molecular Cell)
Source: Molecular Cell - August 11, 2023 Category: Cytology Authors: Min Cao, Alison M. Day, Martin Galler, Heather R. Latimer, Dominic P. Byrne, Thomas W. Foy, Emilia Dwyer, Elise Bennett, Jeremy Palmer, Brian A. Morgan, Patrick A. Eyers, Elizabeth A. Veal Tags: Article Source Type: research
PLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate
The theory was simple. Loss of the PIP3 phosphatase and negative regulator of the PI3K network, PTEN, caused a sustained increase in PIP3/PI3K signaling and hence powered progression of many cancers. Recent work by Chessa et al. supersedes that model. PTEN KO results in massive pathway rewiring and a switch from receptor-dependent to cell-autonomous, self-reinforcing PI3K activation mechanisms. (Source: Molecular Cell)
Source: Molecular Cell - August 10, 2023 Category: Cytology Authors: Tamara A.M. Chessa, Piotr Jung, Arqum Anwar, Sabine Suire, Karen E. Anderson, David Barneda, Anna Kielkowska, Barzan A. Sadiq, Ieng Wai Lai, Sergio Felisbino, Daniel J. Turnham, Helen B. Pearson, Wayne A. Phillips, Junko Sasaki, Takehiko Sasaki, David Oxl Tags: Article Source Type: research
G-quadruplexes associated with R-loops promote CTCF binding
CTCF is a highly conserved protein that is essential for genome organization. Although CTCF recognizes specific DNA sequences, it does not bind to all its potential sites. Wulfridge et al. report that CTCF-bound sites are enriched for R-loops and G-quadruplex chromatin structures. These structures facilitate CTCF binding to promote looping interactions, which contribute to proper gene expression. (Source: Molecular Cell)
Source: Molecular Cell - August 7, 2023 Category: Cytology Authors: Phillip Wulfridge, Qingqing Yan, Nathaniel Rell, John Doherty, Skye Jacobson, Sarah Offley, Sandra Deliard, Kelly Feng, Jennifer E. Phillips-Cremins, Alessandro Gardini, Kavitha Sarma Tags: Article Source Type: research
O-GlcNAcylation of Raptor transduces glucose signals to mTORC1
This study reveals a critical pathway that adds to the intricate mechanisms of glucose-induced mTORC1 activation. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2023 Category: Cytology Authors: Chenchen Xu, Xiaoqing Pan, Dong Wang, Yuanyuan Guan, Wenyu Yang, Xing Chen, Ying Liu Tags: Article Source Type: research
FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways
Huang et al. performed FACS-based CRISPR screens with antibodies recognizing DDR signaling proteins and identified regulators involved in DDR signaling pathways, which demonstrate the feasibility and power of FACS-based screens for the study of signal transduction pathways. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2023 Category: Cytology Authors: Min Huang, Fuwen Yao, Litong Nie, Chao Wang, Dan Su, Huimin Zhang, Siting Li, Mengfan Tang, Xu Feng, Bin Yu, Zhen Chen, Shimin Wang, Ling Yin, Lisha Mou, Traver Hart, Junjie Chen Tags: Resource Source Type: research
NLRP12 senses heme and PAMPs to drive necrotic cell death and inflammation
Red blood cell rupture (hemolysis) activates innate immunity and inflammation by releasing heme. Sundaram et al.1 implicate the immune sensor NLRP12 in hemolytic disease, showing that it controls necrotic cell death induction in response to heme combined with pathogen-associated molecules. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2023 Category: Cytology Authors: Elliott M. Bernard, Petr Broz Tags: Spotlight Source Type: research
Planes, trains, and automobiles: How cells localize their molecules
In this issue of Molecular Cell, Gasparski et al.1 and Loedige et al.2 reshape our understanding of subcellular gene product localization by highlighting the importance of messenger RNA (mRNA) stability and co-translational mechanisms in mRNA and protein localization. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2023 Category: Cytology Authors: Chloe A. Briney, Olivia S. Rissland Tags: Preview Source Type: research
To be (in a transcriptional complex) or not to be (promoting UBR5 ubiquitylation): That is an answer to how degradation controls gene expression
Tsai et al.1 in this issue and Mark et al.2 in Cell reveal how the E3 ligase UBR5 mediates broad regulation by selectively targeting agonist-bound nuclear hormone receptors, MYC, and other transcriptional regulators not incorporated into active gene expression complexes. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2023 Category: Cytology Authors: Laura A. Hehl, Brenda A. Schulman Tags: Preview Source Type: research
Meet the authors: Jianong Zhang and Haojie Huang
Here, Molecular Cell talks to first author Jianong Zhang and co-corresponding author Haojie Huang about their paper, ‘‘A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling’’ (in this issue of Molecular Cell) and their scientific journeys until now. (Source: Molecular Cell)
Source: Molecular Cell - August 3, 2023 Category: Cytology Authors: Jianong Zhang, Haojie Huang Tags: Q & A Source Type: research
Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1
H2A.Z nucleosomes establish the H4K20me2 mark at replication origin through the recruitment of SUV420H1. Huang et al. determined the structure of SUV420H1-H2A.Z/H2A-nucleosome complex, elucidating how SUV420H1 recognizes nucleosomes to ensure site-specific H4K20me2 modification. This provides insights into SUV420H1’s preferential recognition of the H2A.Z nucleosome. (Source: Molecular Cell)
Source: Molecular Cell - August 2, 2023 Category: Cytology Authors: Li Huang, Youwang Wang, Haizhen Long, Haoqiang Zhu, Zengqi Wen, Liwei Zhang, Wenhao Zhang, Zhenqian Guo, Longge Wang, Fangyi Tang, Jie Hu, Keyan Bao, Ping Zhu, Guohong Li, Zheng Zhou Tags: Article Source Type: research
CTCF and R-loops are boundaries of cohesin-mediated DNA looping
CTCF and cohesin organize the 3D eukaryotic genome. Zhang et al. report direct single-molecule and structure evidence that CTCF is a polar cohesin barrier. R-loops are also cohesin barriers and likely play a role in organizing the 3D genome. (Source: Molecular Cell)
Source: Molecular Cell - August 2, 2023 Category: Cytology Authors: Hongshan Zhang, Zhubing Shi, Edward J. Banigan, Yoori Kim, Hongtao Yu, Xiao-chen Bai, Ilya J. Finkelstein Tags: Article Source Type: research
How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication
By determining cryo-EM structures of budding yeast and human replisomes containing the Pol α-primase complex, Jones et al. reveal a conserved mechanism for the coordination of nascent-strand priming in the eukaryotic replisome. The mechanism explains why priming by Pol α-primase is highly efficient on the lagging-strand but not leading-strand template. (Source: Molecular Cell)
Source: Molecular Cell - July 27, 2023 Category: Cytology Authors: Morgan L. Jones, Valentina Aria, Yasemin Baris, Joseph T.P. Yeeles Tags: Article Source Type: research
mRNA location and translation rate determine protein targeting to dual destinations
Protein targeting between destinations can be modulated post-translationally. Using NET1 as a model, Gasparski et al. show that, additionally, mRNA location in the cytoplasm and its translation elongation rate robustly influence protein distribution and function. This effect results from modulating the selection of partners that bind to distinct NET1 domains. (Source: Molecular Cell)
Source: Molecular Cell - July 27, 2023 Category: Cytology Authors: Alexander N. Gasparski, Konstadinos Moissoglu, Sandeep Pallikkuth, Sezen Meydan, Nicholas R. Guydosh, Stavroula Mili Tags: Article Source Type: research
