Meet the authors: Meiling Wang, Wenjing Li, and Weixing Zhao
Molecular Cell talks to co-first authors Meiling Wang and Wenjing Li with co-corresponding author Weixing Zhao about their paper, “Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair” (in this issue of Molecular Cell) and what motivates their scientific pursuits. (Source: Molecular Cell)
Source: Molecular Cell - October 19, 2023 Category: Cytology Authors: Meiling Wang, Wenjing Li, Weixing Zhao Tags: Q & A Source Type: research
Evelyn Witkin: Pioneering DNA repair researcher and social justice activist
Evelyn Maisel Witkin, a brilliant, creative, and inspiring scientist, died July 8, 2023 at the age of 102. Evelyn began studying UV mutagenesis in the 1940s before it was known that genes were composed of DNA. Her pioneering discoveries and amazing mentorship helped reveal the complexity of cellular responses to DNA damage and to define the nascent field of DNA repair. (Source: Molecular Cell)
Source: Molecular Cell - October 19, 2023 Category: Cytology Authors: Carol A. Gross, Graham C. Walker Tags: Obituary Source Type: research
Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller
Wang, Sass et al. determine structures of the CCT-Gβ5-PhLP1 complex that reveal Gβ5 folding intermediates ranging from a molten globule to a fully folded β-propeller. These intermediates define a Gβ5 folding trajectory guided by CCT interactions with surface residues that allow the hydrophobic core to coale sce into its folded state. (Source: Molecular Cell)
Source: Molecular Cell - October 17, 2023 Category: Cytology Authors: Shuxin Wang, Mikaila I. Sass, Yujin Kwon, W. Grant Ludlam, Theresa M. Smith, Ethan J. Carter, Nathan E. Gladden, Margot Riggi, Janet H. Iwasa, Barry M. Willardson, Peter S. Shen Tags: Article Source Type: research
PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly
In this study, Chou et al. discovered that PAICS polyubiquitination induced by cell stresses triggers the recruitment of UBAP2 to confer multivalent interactions for driving phase separation to form purinosome condensates. Melanoma cells are addicted to the constitutive purinosome formation to supply sufficient purines for their proliferation and survival. (Source: Molecular Cell)
Source: Molecular Cell - October 16, 2023 Category: Cytology Authors: Ming-Chieh Chou, Yi-Hsuan Wang, Fei-Yun Chen, Chun-Ying Kung, Kuen-Phon Wu, Jean-Cheng Kuo, Shu-Jou Chan, Mei-Ling Cheng, Chih-Yu Lin, Yu-Chi Chou, Meng-Chiao Ho, Steven Firestine, Jie-rong Huang, Ruey-Hwa Chen Tags: Article Source Type: research
TAK1 is an essential kinase for STING trafficking
Ma, Dang, and Chang et al. uncovered a STING-mediated activation of TAK1 at the ER, which in turn induces STING phosphorylation and initiates STEEP-mediated STING trafficking. These findings shed light on an early signaling event in the regulation of STING exit from ER. (Source: Molecular Cell)
Source: Molecular Cell - October 12, 2023 Category: Cytology Authors: Mingtong Ma, Yifang Dang, Boran Chang, Fei Wang, Junfang Xu, Li Chen, Hang Su, Jinsong Li, Baoxue Ge, Chang Chen, Haipeng Liu Tags: Article Source Type: research
Mitochondrial DNA breaks activate an integrated stress response to reestablish homeostasis
Fu et al. show that mitochondrial DNA double-strand breaks (mtDSBs) severely impair mitochondrial function, affecting mitochondrial protein import and membrane potential. Such damage initiates an integrated stress response (ISR) critical for mitochondrial stability. The study highlights ATAD3A as key in signaling between damaged genomes and the mitochondrial membrane. (Source: Molecular Cell)
Source: Molecular Cell - October 12, 2023 Category: Cytology Authors: Yi Fu, Olivia Sacco, Emily DeBitetto, Evgeny Kanshin, Beatrix Ueberheide, Agnel Sfeir Tags: Article Source Type: research
Sen1 architecture: RNA-DNA hybrid resolution, autoregulation, and insights into SETX inactivation in AOA2
Sen1/SETX helicases resolve RNA-DNA hybrids to regulate transcription, DNA replication, and DNA repair. Appel et al. solve cryo-EM and X-ray crystal structures of Sen1-RNA complexes, showing how the enzyme is auto-regulated, and report how Sen1/SETX can be inactivated by AOA2 RNA-binding cleft mutants. (Source: Molecular Cell)
Source: Molecular Cell - October 12, 2023 Category: Cytology Authors: C. Denise Appel, Oya Bermek, Venkata P. Dandey, Makayla Wood, Elizabeth Viverette, Jason G. Williams, Jonathan Bouvette, Amanda A. Riccio, Juno M. Krahn, Mario J. Borgnia, R. Scott Williams Tags: Article Source Type: research
DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of lamin A/C
Homologous-recombination-deficient (HRD) tumors often develop resistance to traditional chemotherapies, making them difficult to kill. Kovacs et al. find that HRD tumor cells exhibit DNA-damage-induced nuclear envelope (NE) rupture and subsequent NE vulnerability. Targeting this structural vulnerability could potentially provide a complement to traditional, DNA-damage-based chemotherapies. (Source: Molecular Cell)
Source: Molecular Cell - October 12, 2023 Category: Cytology Authors: Marton Tibor Kovacs, Marie Vallette, Pauline Wiertsema, Florent Dingli, Damarys Loew, Guilherme Pedreira de Freitas Nader, Matthieu Piel, Raphael Ceccaldi Tags: Article Source Type: research
DICER ribonuclease removes harmful R-loops
R-loops, consisting of a DNA-RNA hybrid and a displaced DNA strand, can compromise genome integrity. Thus far, only type H RNases are known to cleave RNA within DNA-RNA hybrids and R-loops. Camino and Dutta et al. show that DICER RNase cleaves RNA within the context of R-loops. (Source: Molecular Cell)
Source: Molecular Cell - October 11, 2023 Category: Cytology Authors: Lola P. Camino, Arijit Dutta, Sonia Barroso, Carmen P érez-Calero, Jeffrey N. Katz, María García-Rubio, Patrick Sung, Belén Gómez-González, Andrés Aguilera Tags: Article Source Type: research
The structural mechanism of dimeric DONSON in replicative helicase activation
Cvetkovic, Passaretti, et al. determine the cryo-EM structure of a double CMG bound by dimeric DONSON, explaining how the CMG helicase is assembled symmetrically in metazoans. MCM rings become misaligned and poised to cross paths supporting replication origin activation. Disrupting DONSON dimer affects DNA replication, exp laining etiology of primordial dwarfism. (Source: Molecular Cell)
Source: Molecular Cell - October 10, 2023 Category: Cytology Authors: Milos A. Cvetkovic, Paolo Passaretti, Agata Butryn, Alicja Reynolds-Winczura, Georgia Kingsley, Aggeliki Skagia, Cyntia Fernandez-Cuesta, Divyasree Poovathumkadavil, Roger George, Anoop S. Chauhan, Satpal S. Jhujh, Grant S. Stewart, Agnieszka Gambus, Ales Tags: Article Source Type: research
N6-methyladenosine in 7SK small nuclear RNA underlies RNA polymerase II transcription regulation
Wang et al. discovered that 7SK RNA contains high levels of m6A in lung cancer cells. METTL3 and ALKBH5 modify 7SK at eight different m6A sites. Removal of m6A induces 7SK conformational change and sequesters P-TEFb, leading to RNA Pol II promoter-proximal pausing, inhibited transcription, and cancer cell growth. (Source: Molecular Cell)
Source: Molecular Cell - October 10, 2023 Category: Cytology Authors: Yuzhi Wang, Conner M. Traugot, Jodi L. Bubenik, Tianqi Li, Peike Sheng, Nicholas M. Hiers, Paul Fernandez, Lu Li, Jiang Bian, Maurice S. Swanson, Mingyi Xie Tags: Article Source Type: research
Establishment of dsDNA-dsDNA interactions by the condensin complex
Tang et al. biochemically explore how the condensin complex promotes chromosome compaction during cell divisions, revealing that single condensins sequentially and topologically capture two double-stranded DNAs. The authors uncover a DNA-DNA capture signature in vivo, indicative of a “diffusion capture ” mechanism for mitotic chromosome formation. (Source: Molecular Cell)
Source: Molecular Cell - October 10, 2023 Category: Cytology Authors: Minzhe Tang, Georgii Pobegalov, Hideki Tanizawa, Zhuo A. Chen, Juri Rappsilber, Maxim Molodtsov, Ken-ichi Noma, Frank Uhlmann Tags: Article Source Type: research
APE1-dependent base excision repair of DNA photodimers in human cells
Gautam et al. show for the first time the existence of an alternative pathway to repair UV-induced DNA damage (photodimers) in normal human cells. This pathway functions additively but independently of NER and is human equivalent of the evolutionary-ancient base excision repair-dependent mechanism reported in bacteriophage and some bacteria. (Source: Molecular Cell)
Source: Molecular Cell - October 9, 2023 Category: Cytology Authors: Amit Gautam, Heather Fawcett, Kamila Burdova, Jan Brazina, Keith W. Caldecott Tags: Article Source Type: research
tRNA renovatio: Rebirth through fragmentation
Kuhle et al. explore tRNA-derived small RNAs (tsRNAs) as critical cellular regulators. Originating from tRNA “renovatio” (Latin for “renewal and rebirth”), tsRNA functions are tied to 3D structures and dynamically regulated by RNA modifications and binding partners, highlighting the promise of experimental and AI-based approaches to tackle their biological complexity. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Bernhard Kuhle, Qi Chen, Paul Schimmel Tags: Review Source Type: research
A fluorophore-conjugated reagent enabling rapid detection, isolation and live tracking of senescent cells
Magkouta et al. describe a marker for senescence detection (GLF16) that surpasses limitations of previously established markers (SA-β-Gal and GL13). Apart from in vitro analyses, GLF16 is particularly suitable for in vivo identification, isolation, and downstream characterization of senescent cell populati ons at the single-cell level in various biological materials. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Sophia Magkouta, Dimitris Veroutis, Athanasios Pousias, Angelos Papaspyropoulos, Natassa Pippa, Nikolaos Lougiakis, Konstantinos Kambas, Nefeli Lagopati, Aikaterini Polyzou, Maria Georgiou, Maria Chountoulesi, Stergios Pispas, Spyros Foutadakis, Nicole Po Tags: Technology Source Type: research
