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How similar are the molecular mechanisms of yeast and metazoan genome replication initiation?
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-03-07 DOI: 10.1042/BST20220917
Giacomo Palm, Alessandro Costa
{"title":"How similar are the molecular mechanisms of yeast and metazoan genome replication initiation?","authors":"Giacomo Palm, Alessandro Costa","doi":"10.1042/BST20220917","DOIUrl":"https://doi.org/10.1042/BST20220917","url":null,"abstract":"<p><p>DNA replication start sites are licensed for replication when two hexameric ring-shaped motors of the replicative helicase are loaded as an inactive double hexamer around duplex DNA. Activation requires untwisting of the double helix and ejection of one DNA strand from the central channel of each helicase ring. The process of replication initiation is best understood in yeast, thanks to reconstitution with purified yeast proteins, which allowed systematic structural analysis of the replication initiation process. Orthologs of most yeast replication factors have been identified in higher eukaryotes; however, reconstitution of metazoan replication initiation is still in its infancy, with double hexamer loading but not activation having been achieved. Nonetheless, artificial intelligence-driven structure prediction and cryo-EM studies on native complexes, combined with cell-based and cell-free approaches, are starting to provide insights into metazoan replication initiation mechanisms. Here, we describe the emerging picture.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
How does the tubulin code facilitate directed cell migration?
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-21 DOI: 10.1042/BST20240841
Miguel Marques Simoes-da-Silva, Marin Barisic
{"title":"How does the tubulin code facilitate directed cell migration?","authors":"Miguel Marques Simoes-da-Silva, Marin Barisic","doi":"10.1042/BST20240841","DOIUrl":"https://doi.org/10.1042/BST20240841","url":null,"abstract":"<p><p>Besides being a component of the cytoskeleton that provides structural integrity to the cell, microtubules also serve as tracks for intracellular transport. As the building units of the mitotic spindle, microtubules distribute chromosomes during cell division. By distributing organelles, vesicles, and proteins, they play a pivotal role in diverse cellular processes, including cell migration, during which they reorganize to facilitate cell polarization. Structurally, microtubules are built up of α/β-tubulin dimers, which consist of various tubulin isotypes that undergo multiple post-translational modifications (PTMs). These PTMs allow microtubules to differentiate into functional subsets, influencing the associated processes. This text explores the current understanding of the roles of tubulin PTMs in cell migration, particularly detyrosination and acetylation, and their implications in human diseases.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The cellular basis of meristem development in fern gametophytes.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-13 DOI: 10.1042/BST20240728
Chong Xie, Cankui Zhang, Xing Liu, Yun Zhou
{"title":"The cellular basis of meristem development in fern gametophytes.","authors":"Chong Xie, Cankui Zhang, Xing Liu, Yun Zhou","doi":"10.1042/BST20240728","DOIUrl":"https://doi.org/10.1042/BST20240728","url":null,"abstract":"<p><p>The life cycle of land plants is characterized by alternating generations of sexual gametophytes and asexual sporophytes. Unlike seed plants, seed-free vascular plants, including ferns, initiate and maintain pluripotent meristems during their gametophyte phase to sustain body expansion and drive the formation of sexual organs for reproduction. This review summarizes meristem development among various fern species during the gametophyte phase, focusing on the cellular basis of meristem initiation, proliferation, and termination. We review the different types of gametophytic meristems in ferns, including apical cell (AC)-based meristems, multicellular apical meristems, and multicellular marginal meristems. We highlight both conserved and lineage-specific patterns of cell division, which are closely associated with these meristem identities and play crucial roles in shaping gametophytic morphology. Additionally, we highlight recent progress in understanding the dynamics of cell division and growth that drive meristem development, through studies that integrate confocal live imaging and computational quantitative analysis. Furthermore, we discuss the influence of environmental and genetic factors on cell division activity in fern gametophytes, including conserved transcriptional regulators that sustain meristem indeterminacy and proliferation in the model fern Ceratopteris richardii.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PIEZO channels as multimodal mechanotransducers. 作为多模式机械换能器的 PIEZO 通道。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-12 DOI: 10.1042/BST20240419
Jérôme J Lacroix, Tharaka D Wijerathne
{"title":"PIEZO channels as multimodal mechanotransducers.","authors":"Jérôme J Lacroix, Tharaka D Wijerathne","doi":"10.1042/BST20240419","DOIUrl":"https://doi.org/10.1042/BST20240419","url":null,"abstract":"<p><p>All living beings experience a wide range of endogenous and exogenous mechanical forces. The ability to detect these forces and rapidly convert them into specific biological signals is essential to a wide range of physiological processes. In vertebrates, these fundamental tasks are predominantly achieved by two related mechanosensitive ion channels called PIEZO1 and PIEZO2. PIEZO channels are thought to sense mechanical forces through flexible transmembrane blade-like domains. Structural studies indeed show that these mechanosensory domains adopt a curved conformation in a resting membrane but become flattened in a membrane under tension, promoting an open state. Yet, recent studies suggest the intriguing possibility that distinct mechanical stimuli activate PIEZO channels through discrete molecular rearrangements of these domains. In addition, biological signals downstream of PIEZO channel activation vary as a function of the mechanical stimulus and of the cellular context. These unique features could explain how PIEZOs confer cells the ability to differentially interpret a complex landscape of mechanical cues.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lysine acetylation in cyanobacteria: emerging mechanisms and functions.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-12 DOI: 10.1042/BST20241037
Xin Liu, Mingkun Yang, Feng Ge, Jindong Zhao
{"title":"Lysine acetylation in cyanobacteria: emerging mechanisms and functions.","authors":"Xin Liu, Mingkun Yang, Feng Ge, Jindong Zhao","doi":"10.1042/BST20241037","DOIUrl":"https://doi.org/10.1042/BST20241037","url":null,"abstract":"<p><p>Cyanobacteria are ancient and abundant photosynthetic prokaryotes that play crucial roles in global carbon and nitrogen cycles. They exist in a variety of environments and have been used extensively as model organisms for studies of photosynthesis and environmental adaptation. Lysine acetylation (Kac), a widespread and evolutionarily conserved protein posttranslational modification, is reversibly catalyzed by lysine acetyltransferases (KAT) and lysine deacetylases (KDACs). Over the past decade, a growing number of acetylated proteins have been identified in cyanobacteria, and Kac is increasingly recognized as having essential roles in many cellular processes, such as photosynthesis, energy metabolism, and stress responses. Recently, cGNAT2 and CddA were identified as KAT and KDAC in the model cyanobacterium Synechococcus sp. PCC 7002, respectively. The identified Kac regulatory enzymes provide novel insight into the mechanisms that globally regulate photosynthesis in cyanobacteria and potentially other photosynthetic organisms. This review summarizes recent progress in our understanding of the functions and mechanisms of lysine acetylation in Cyanobacteria. The challenges and future perspectives in this field are also discussed.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Progress toward a comprehensive brain protein interactome. 建立全面的大脑蛋白质相互作用组的进展。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-12 DOI: 10.1042/BST20241135
Vy Dang, Brittney Voigt, Edward M Marcotte
{"title":"Progress toward a comprehensive brain protein interactome.","authors":"Vy Dang, Brittney Voigt, Edward M Marcotte","doi":"10.1042/BST20241135","DOIUrl":"https://doi.org/10.1042/BST20241135","url":null,"abstract":"<p><p>Protein-protein interactions (PPIs) in the brain play critical roles across all aspects of the central nervous system, from synaptic transmission, glial development, myelination, to cell-to-cell communication, and more. Understanding these interactions is crucial for deciphering neurological mechanisms and the underlying biochemical machinery affected in neurological disorders. Recently, advances in proteomics techniques have significantly enhanced our ability to study interactions among the proteins expressed in the brain. Here, we review some of the high-throughput studies characterizing brain PPIs, using affinity purification, proximity labeling, co-fractionation, and chemical cross-linking mass spectrometry methods, as well as yeast two-hybrid assays. We present the current state of the field, discuss challenges, and highlight promising future directions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
'Where is my gap': mechanisms underpinning PARP inhibitor sensitivity in cancer.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-10 DOI: 10.1042/BST20241633
Lauryn Buckley-Benbow, Alessandro Agnarelli, Roberto Bellelli
{"title":"'Where is my gap': mechanisms underpinning PARP inhibitor sensitivity in cancer.","authors":"Lauryn Buckley-Benbow, Alessandro Agnarelli, Roberto Bellelli","doi":"10.1042/BST20241633","DOIUrl":"https://doi.org/10.1042/BST20241633","url":null,"abstract":"<p><p>The introduction of poly-ADP ribose polymerase (PARP) inhibitors (PARPi) has completely changed the treatment landscape of breast cancer susceptibility 1-2 (BRCA1-BRCA2)-mutant cancers and generated a new avenue of research in the fields of DNA damage response and cancer therapy. Despite this, primary and secondary resistances to PARPi have become a challenge in the clinic, and novel therapies are urgently needed to address this problem. After two decades of research, a unifying model explaining sensitivity of cancer cells to PARPi is still missing. Here, we review the current knowledge in the field and the increasing evidence pointing to a crucial role for replicative gaps in mediating sensitization to PARPi in BRCA-mutant and 'wild-type' cancer cells. Finally, we discuss the challenges to be addressed to further improve the utilization of PARPi and tackle the emergence of resistance in the clinical context.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Conformational dynamics of the nuclear pore complex central channel.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-07 DOI: 10.1042/BST20240507
Yu Chen, Guoli Zhou, Miao Yu
{"title":"Conformational dynamics of the nuclear pore complex central channel.","authors":"Yu Chen, Guoli Zhou, Miao Yu","doi":"10.1042/BST20240507","DOIUrl":"https://doi.org/10.1042/BST20240507","url":null,"abstract":"<p><p>The nuclear pore complex (NPC) is a vital regulator of molecular transport between the nucleus and cytoplasm in eukaryotic cells. At the heart of the NPC's function are intrinsically disordered phenylalanineglycine-rich nucleoporins (FG-Nups), which form a dynamic permeability barrier within the central channel. This disordered nature facilitates efficient nucleocytoplasmic transport but also poses significant challenges to its characterization, especially within the nano-confined environment of the NPC. Recent advances in experimental techniques, such as cryo-electron microscopy, atomic force microscopy, fluorescence microscopy, and nuclear magnetic resonance, along with computational modeling, have illuminated the conformational flexibility of FG-Nups, which underpins their functional versatility. This review synthesizes these advancements, emphasizing how disruptions in FG-Nup behavior-caused by mutations or pathological interactions-contribute to diseases such as neurodegenerative disorders, aging-related decline, and viral infections. Despite progress, challenges persist in deciphering FG-Nup dynamics within the crowded and complex cellular environment, especially under pathological conditions. Addressing these gaps is critical for advancing therapeutic strategies targeting NPC dysfunction in disease progression.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polymer models of chromatin organization in virally infected cells.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-07 DOI: 10.1042/BST20240598
Andrea Fontana, Fabrizio Tafuri, Alex Abraham, Simona Bianco, Andrea Esposito, Mattia Conte, Francesca Vercellone, Florinda Di Pierno, Sougata Guha, Ciro Di Carluccio, Andrea M Chiariello
{"title":"Polymer models of chromatin organization in virally infected cells.","authors":"Andrea Fontana, Fabrizio Tafuri, Alex Abraham, Simona Bianco, Andrea Esposito, Mattia Conte, Francesca Vercellone, Florinda Di Pierno, Sougata Guha, Ciro Di Carluccio, Andrea M Chiariello","doi":"10.1042/BST20240598","DOIUrl":"10.1042/BST20240598","url":null,"abstract":"<p><p>Genome architecture is closely tied to essential biological functions, yet a complete understanding of the mechanisms governing DNA folding remains a significant challenge. Theoretical models based on polymer physics have been applied to decipher the complexity of chromatin architecture and uncover the physical processes shaping its structure. Importantly, recent findings suggest that certain viruses can alter the 3D organization of the host genome. In this review, we highlight recent advances in the development of polymer models used to study how chromatin 3D structure within a cell re-organizes following viral infection, with a particular emphasis on the SARS-CoV-2 virus, capable of altering genome organization of the host cell at different scales, including A/B compartments, TADs and gene-enhancer regulatory contacts.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in nanobody multimerization and multispecificity: from in vivo assembly to in vitro production.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-07 DOI: 10.1042/BST20241419
Mohammed Al-Seragi, Yilun Chen, Franck Duong van Hoa
{"title":"Advances in nanobody multimerization and multispecificity: from in vivo assembly to in vitro production.","authors":"Mohammed Al-Seragi, Yilun Chen, Franck Duong van Hoa","doi":"10.1042/BST20241419","DOIUrl":"https://doi.org/10.1042/BST20241419","url":null,"abstract":"<p><p>NANOBODIES® (Nbs) have emerged as valuable tools across therapeutic, diagnostic, and industrial applications owing to their small size and consequent ability to bind unique epitopes inaccessible to conventional antibodies. While Nbs retrieved from immune libraries normally possess sufficient affinity and specificity for their cognate antigens in the practical use case, their multimerization will often increase functional affinity via avidity effects. Therefore, to rescue binding affinity and broaden targeting specificities, recent efforts have focused on conjugating multiple Nb clones - of identical or unique antigen cognates - together. In vivo and in vitro approaches, including flexible linkers, antibody domains, self-assembling coiled coils, chemical conjugation, and self-clustering hydrophobic sequences, have been employed to produce multivalent and multispecific Nb constructs. Examples of successful Nb multimerization are diverse, ranging from immunoassaying reagents to virus-neutralizing moieties. This review aims to recapitulate the in vivo and in vitro modalities to produce multivalent and multispecific Nbs while highlighting the applications, advantages, and drawbacks tied to each method.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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