Molecular Cell最新文献_第5页

Conserved and divergent mitochondrial assemblies in kinetoplastid parasites 着丝体寄生虫中保守的和发散的线粒体组合

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.08.031

Md Solayman,Yi-Ting Liao,Sarah E. Calvo,Andres F. Vacas,Malvina Papanastasiou,Keith D. Rivera,D.R. Mani,Brian W. Boyle,Felicia G. Deng,MitoCarta Tree of Life Consortium,Namrata D. Udeshi,Vamsi K. Mootha,Inna Aphasizheva,Luke H. Chao,Ruslan Aphasizhev

{"title":"Conserved and divergent mitochondrial assemblies in kinetoplastid parasites","authors":"Md Solayman,Yi-Ting Liao,Sarah E. Calvo,Andres F. Vacas,Malvina Papanastasiou,Keith D. Rivera,D.R. Mani,Brian W. Boyle,Felicia G. Deng,MitoCarta Tree of Life Consortium,Namrata D. Udeshi,Vamsi K. Mootha,Inna Aphasizheva,Luke H. Chao,Ruslan Aphasizhev","doi":"10.1016/j.molcel.2026.08.031","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.08.031","url":null,"abstract":"The mitochondrial proteomes of Leishmania tarentolae and Trypanosoma brucei contain ∼1,700 proteins, most of which lack homologs in higher eukaryotes. Here, we integrate complexome profiling and cryo-electron microscopy to define conserved and lineage-specific macromolecular assemblies that support mitochondrial functions in these kinetoplastid protozoa. Comparative analyses reveal species- and life-stage-dependent differences in the abundance and composition of respiratory, metabolic, RNA processing, and other complexes, refining and expanding current annotations. Structures of L. tarentolae respiratory complex III2 (CIII2), complex IV2 (CIV2), and complex V (CV) identify nine previously unrecognized nuclear-encoded subunits and resolve five mitochondrially encoded proteins, including products of pan-edited mRNAs. These reconstructions uncover architectural innovations: a subunit 8 of ubiquinol cytochrome-c reductase (QCR8) N-terminal extension that plugs the vestigial mitochondrial processing peptidase (MPP)α/β cavity in CIII2, a CIV2 dimer stabilized by an extensive clade-restricted interface, and a CV dimer containing the mitochondrially encoded ATP6 subunit. Together, our findings reveal how kinetoplastids assemble specialized mitochondrial machinery while incorporating diverged components into core modules shared across eukaryotes.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"3 1","pages":"4043-4057.e7"},"PeriodicalIF":16.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

ZNFX1, an immunoregulatory RNA helicase and E3 ubiquitin ligase, assembles into pleiomorphic polymers ZNFX1，一种免疫调节RNA解旋酶和E3泛素连接酶，组装成多形性聚合物

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.09.002

Katerina Naydenova,Thomas Mund,Matthew C.J. Yip,Ceara M. Harper,Kendra E. Leigh,Jacqueline Hankinson,Keith B. Boyle,Alexander Heatley,Elsje G. Otten,Valeria Lulla,Yorgo Modis,Felix Randow

{"title":"ZNFX1, an immunoregulatory RNA helicase and E3 ubiquitin ligase, assembles into pleiomorphic polymers","authors":"Katerina Naydenova,Thomas Mund,Matthew C.J. Yip,Ceara M. Harper,Kendra E. Leigh,Jacqueline Hankinson,Keith B. Boyle,Alexander Heatley,Elsje G. Otten,Valeria Lulla,Yorgo Modis,Felix Randow","doi":"10.1016/j.molcel.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.09.002","url":null,"abstract":"NFX1-type zinc-finger-containing 1 (ZNFX1) is an SF1-family RNA helicase essential for innate immunity. Patients with ZNFX1 mutations experience recurrent infections, yet the underlying mechanism remains unclear. We determined cryo-electron microscopy (cryo-EM) structures of RNA-bound and RNA-free ZNFX1 and revealed auto-inhibition of the helicase-associated ATPase through a regulatory insertion occluding the RNA-binding groove. ZNFX1 also functions as a bi-catalytic E3 ubiquitin ligase, containing an RZ finger homologous to RNF213 and a previously unidentified Miz-like domain, which cooperate in catalyzing ubiquitylation. Ubiquitin chains enhance E3 activity further. Patient mutations demonstrate that the helicase/ATPase, E3 ligase, and the rigid zinc-finger stalk connecting them are required for function. ZNFX1 can assemble into structured, pleiomorphic polymers fostering trans-auto-ubiquitylation; understanding this reveals a mechanism that controls ZNFX1 stability and may facilitate RNA sequestration in stress granules and antiviral activity. These findings establish ZNFX1 as a multifunctional enzyme in immunity that couples RNA sensing to ubiquitin signaling and assembles into higher-order structures for signal amplification.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"92 1","pages":"4018-4031.e4"},"PeriodicalIF":16.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 early RNA decay factor ZC3H18 directs first intron splicing 早期RNA衰变因子ZC3H18指导第一个内含子剪接

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-29 DOI: 10.1016/j.molcel.2026.09.009

Marion Le Rest,Nour El Houda Benbahouche,Christopher Cyrus Kuhn,Jérôme Rouvière,Lis Jakobsen,Marie-Cécile Robert,Julie Abrino,Om Rathore,Yujia Zhang,Andrii Bugai,Céline Verheggen,William Garland,Jens S. Andersen,Elena Conti,Edouard Bertrand,Torben Heick Jensen

{"title":"The early RNA decay factor ZC3H18 directs first intron splicing","authors":"Marion Le Rest,Nour El Houda Benbahouche,Christopher Cyrus Kuhn,Jérôme Rouvière,Lis Jakobsen,Marie-Cécile Robert,Julie Abrino,Om Rathore,Yujia Zhang,Andrii Bugai,Céline Verheggen,William Garland,Jens S. Andersen,Elena Conti,Edouard Bertrand,Torben Heick Jensen","doi":"10.1016/j.molcel.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.09.009","url":null,"abstract":"Pre-mRNA splicing is essential for gene expression. In human cells, the cap-binding complex (CBC) has long been known to facilitate first intron splicing, but it is by an unknown mechanism. The CBC also promotes early RNA decay by recruiting the nuclear exosome targeting (NEXT) complex via the linker proteins ARS2 and ZC3H18. How the CBC orchestrates these opposite activities is elusive. Here, we show that ZC3H18 interacts with three splicing factors, PRPF40A, PRP4K, and FNBP4, to stimulate first intron splicing genome wide. Linking this unexpected function of ZC3H18 to the CBC, disruption of the CBC-ARS2-ZC3H18 axis corrupts first intron splicing. Although ZC3H18 acts in both RNA decay and splicing, its association with splicing factors is mutually exclusive with its binding to NEXT. Our results rationalize cap-stimulated first intron splicing mechanistically and suggest that splicing factors displace NEXT from ZC3H18, designating the nascent RNA to a productive pathway at the expense of RNA decay.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"10 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Transcription factor clusters enhance gene expression in vivo without modulating bursting dynamics 转录因子簇增强基因在体内的表达而不调节爆发动力学

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-29 DOI: 10.1016/j.molcel.2026.09.011

Emilia Cadar,Anthony Birnie,Richard Marsman,Rianne Grond,Jacques P. Bothma

{"title":"Transcription factor clusters enhance gene expression in vivo without modulating bursting dynamics","authors":"Emilia Cadar,Anthony Birnie,Richard Marsman,Rianne Grond,Jacques P. Bothma","doi":"10.1016/j.molcel.2026.09.011","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.09.011","url":null,"abstract":"Phase separation drives key cellular processes, yet the role transcription factor condensates play in gene regulation remains contested. Evidence comes primarily from in vitro experiments, leaving it largely unknown how these structures regulate transcription in vivo. To address this knowledge gap, we used cutting-edge microscopy to measure and manipulate transcription in live Drosophila embryos. Here, we show that Dorsal (an NF-κB homolog) forms clusters that associate with a subset of endogenous target genes. We demonstrate that binding-site abundance governs cluster-gene association, which in turn amplifies transcription. Moreover, enhancer mutations that specifically disrupt cluster-gene association cause lethal developmental defects. Through precise spatiotemporal control of Dorsal concentration, we uncovered that Dorsal clusters neither initiate nor sustain transcriptional bursts. Instead, they only augment polymerase loading during a burst. Our findings establish that Dorsal clusters have a function in vivo, while fundamentally challenging prevailing models of how clusters, hubs, or condensates regulate transcription.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"1 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

ATM safeguards DNA replication by restraining pathological repriming at endogenous base lesions ATM通过抑制内源性碱基损伤的病理复核来保护DNA复制

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-28 DOI: 10.1016/j.molcel.2026.09.006

Lucia Sommerova,Ashleigh King,J. Ross Chapman

{"title":"ATM safeguards DNA replication by restraining pathological repriming at endogenous base lesions","authors":"Lucia Sommerova,Ashleigh King,J. Ross Chapman","doi":"10.1016/j.molcel.2026.09.006","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.09.006","url":null,"abstract":"Poly(ADP-ribose) polymerase inhibitors (PARPi) exploit homologous recombination (HR) deficiency in BRCA1/2-mutant cancers to induce synthetic lethality. PARPi also kill ataxia telangiectasia-mutated (ATM)-deficient cells, but the underlying mechanism has remained unclear. Here, we define the mechanism of PARPi cytotoxicity in mammalian ATM-deficient cells, uncovering a critical role for ATM in DNA replication. In the absence of ATM, unrestrained PRIMPOL-dependent repriming at oxidative base lesions generates post-replicative DNA gaps that activate PARP. This defect is driven by aberrant BRCA1-A recruitment to stalled replication forks in ATM-deficient cells, suppressing HLTF/ZRANB3-mediated replication fork slowing. These DNA gaps require HR for repair and underlie PARPi synthetic lethality. Suppressing repriming or base excision repair, or reducing oxidative stress, alleviates these defects. Our findings reveal how spontaneous oxidative DNA damage synergizes with dysregulated replication to drive PARPi sensitivity, establishing a paradigm of post-replicative repair addiction in ATM-deficient cells and linking oxidative DNA damage to genome instability in ataxia telangiectasia.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"17 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Simplifying in silico protein evolution with minimal screening by unZipro 简化硅蛋白进化与最小筛选的unZipro

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-24 DOI: 10.1016/j.molcel.2026.08.028

Zhaohui Qin,Sanzeng Zhao,Zhaolong Deng,Xiaomin Si,Cheng Xing,Zhenfei Zhang,Yumeng Zhang,Xueying Han,Jindong Zhang,Yang Chen,Xiaoyi Liu,Jinhui Li,Lei Fu,Liyuan You,James W. Murray,Huiyun Liu,Huifang Li,Chengwei Li,Song Wu,Junzhou Li,Zhen Chen,Jiangning Song,Daowen Wang,Xiang Ji

{"title":"Simplifying in silico protein evolution with minimal screening by unZipro","authors":"Zhaohui Qin,Sanzeng Zhao,Zhaolong Deng,Xiaomin Si,Cheng Xing,Zhenfei Zhang,Yumeng Zhang,Xueying Han,Jindong Zhang,Yang Chen,Xiaoyi Liu,Jinhui Li,Lei Fu,Liyuan You,James W. Murray,Huiyun Liu,Huifang Li,Chengwei Li,Song Wu,Junzhou Li,Zhen Chen,Jiangning Song,Daowen Wang,Xiang Ji","doi":"10.1016/j.molcel.2026.08.028","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.08.028","url":null,"abstract":"Despite the significant progress made in recent years, current AI-driven protein engineering methods often suffer from iterative experimental validation, limited success rates, modest improvements, and/or high computational costs. Moreover, their utility for evolving plant proteins remains unexplored. Here we present unZipro, an efficient, scalable, and generalizable framework for zero-shot, in silico protein evolution. unZipro integrates a compact, pre-trained inverse folding model with meta-learning to derive family-specific fitness landscapes. We demonstrate unZipro’s ability to directly identify high-activity variants from minimal libraries (∼10 candidates) with an average success rate of 61% across nine diverse proteins, achieving up to a 28-fold increase in the gene-editing activity of T5E-CasΦ2 fusion variants. Leveraging unZipro, we developed state-of-the-art plant gene-editing nucleases, superior firefly luciferase variants, enhanced rice transcription factors, and barley-derived antiviral proteins with elevated potency. Overall, unZipro represents a new paradigm for cost-effective, widely accessible, and transformative protein engineering in biology, biotechnology, and agriculture.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"162 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

CaMKII monomers are sufficient for GluN2B binding, co-condensation, and synaptic potentiation CaMKII单体足以结合GluN2B、共缩合和突触增强

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-23 DOI: 10.1016/j.molcel.2026.08.029

Carolyn Nicole Brown,C. Madison Barker,Carley N. Miller,Fan-Yi Chao,Jason Aoto,Steven J. Coultrap,K. Ulrich Bayer

{"title":"CaMKII monomers are sufficient for GluN2B binding, co-condensation, and synaptic potentiation","authors":"Carolyn Nicole Brown,C. Madison Barker,Carley N. Miller,Fan-Yi Chao,Jason Aoto,Steven J. Coultrap,K. Ulrich Bayer","doi":"10.1016/j.molcel.2026.08.029","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.08.029","url":null,"abstract":"Cognitive functions require synaptic plasticity, specifically long-term potentiation (LTP). LTP is thought to require Ca2+/CaM-dependent protein kinase II (CaMKII) binding to the NMDA-type glutamate receptor subunit GluN2B, but this poses a conundrum: truncated CaMKII monomers (without the hub domain that forms 12meric holoenzymes) fail to bind GluN2B within cells but still potentiate synapses when made constitutively active. We hypothesized that CaMKII monomer binding to GluN2B has just eluded detection. Instead, even though full-length CaMKII monomers (with hub-domain mutations) were found to indeed bind and even form condensates with GluN2B, truncated monomers were not. Nonetheless, truncated monomers still potentiated synapses, even in neurons with GluN2B mutations that ablate CaMKII binding. However, potentiation occurred only with monomers that were made Ca2+-independent by artificial phosphatase-resistant thio-autophosphorylation, not by regular autophosphorylation of T286. These findings support that CaMKII binding to GluN2B is required during physiological LTP induction because it generates the phosphatase-resistant autonomous activity that mediates LTP expression.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"7 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Linker histone H1.0 loads onto nucleosomes through multiple pathways that are facilitated by histone chaperones 连接体组蛋白H1.0通过多种途径加载到核小体上，这些途径由组蛋白伴侣促进

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-22 DOI: 10.1016/j.molcel.2026.09.001

Ehsan Akbari,Nathaniel L. Burge,Matti Valdimarsson,Aritra Chowdhury,Benjamin Schuler,Michael G. Poirier

{"title":"Linker histone H1.0 loads onto nucleosomes through multiple pathways that are facilitated by histone chaperones","authors":"Ehsan Akbari,Nathaniel L. Burge,Matti Valdimarsson,Aritra Chowdhury,Benjamin Schuler,Michael G. Poirier","doi":"10.1016/j.molcel.2026.09.001","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.09.001","url":null,"abstract":"Linker histone H1 is an essential chromatin architectural protein that compacts chromatin into transcriptionally silent regions by interacting with nucleosomal and linker DNA while rapidly exchanging in vivo. How H1 targets nucleosomes while being dynamic remains unanswered. Using a single-molecule strategy, we investigated human H1.0 interactions with DNA and nucleosomes. H1.0 directly binds nucleosomes and naked DNA with a preference toward nucleosomes. DNA-bound H1.0 exhibited a range of bound lifetimes with both mobile and immobile states, where H1.0 was largely mobile, diffused over kilobase distances in seconds, but surprisingly did not load onto nucleosomes. Linker histone chaperones significantly facilitated H1.0-nucleosome loading by enabling H1.0 loading through DNA sliding, reducing DNA resident times without impacting nucleosome resident times, increasing mobility along DNA, and targeting H1.0 loading onto the nucleosome dyad. These findings reveal the multiple distinct mechanisms linker histones and their chaperones use to interact with nucleosomes to regulate chromatin accessibility.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"18 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

De novo-engineered guide RNA-directed transposition with TnpB-family proteins 用tnpb家族蛋白重新设计引导rna定向转位

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-17 DOI: 10.1016/j.molcel.2026.08.023

Richard D. Schargel,Laura Chacon Machado,Shravanika Kumaran,Jordan E. Thesier,Shreya S. Krishnan,Alba Guarné,Joseph E. Peters

{"title":"De novo-engineered guide RNA-directed transposition with TnpB-family proteins","authors":"Richard D. Schargel,Laura Chacon Machado,Shravanika Kumaran,Jordan E. Thesier,Shreya S. Krishnan,Alba Guarné,Joseph E. Peters","doi":"10.1016/j.molcel.2026.08.023","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.08.023","url":null,"abstract":"Programmable DNA integration using CRISPR-associated transposase elements (CASTs) offers powerful capabilities for genome engineering. The large single effector Cas12k CAST examples evolved from a minimal TnpB nuclease protein. Here, we engineer a de novo RNA-guided transposition systems in bacteria, where the single guide RNA effector components are repurposed nuclease-dead TnpB-family proteins. These compact systems mediate high-efficiency guide-RNA-directed DNA insertion with preserved orientation control, target immunity, and release of a host factor requirement and can be paired with an exonuclease domain to mediate cut-and-paste transposition. In this engineered context, the TnpB derivatives show features not predicted from the original enzymes, suggesting untapped avenues for improvement. In parallel, we show that mutations at the TniQ-TnsC interface in the Cas12k CAST system selectively attenuate off-site insertions while enhancing on-site activity. These results establish how Cas12 proteins and antecedent TnpB proteins can be engineered for high performance and specificity with guide-RNA-directed systems.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"59 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Yeast Rad55-Rad57-SHU paralog complex dynamically promotes Rad51 filament formation. 酵母Rad55-Rad57-SHU平行复合体动态促进Rad51细丝的形成。

IF 16 1区生物学

Molecular Cell Pub Date : 2026-09-17 Epub Date: 2026-07-21 DOI: 10.1016/j.molcel.2026.06.045

Christopher W Koo, Steven K Gore, Soo Y Ro, Jie Liu, Christine Yu, Caleigh M Azumaya, Bobby Brillantes, Inna Zilberleyb, Henry Chen, Mariam B Rafiqzada, Lyra Garcia Sanchez, Wolf-Dietrich Heyer, Claudio Ciferri, Stanislau Yatskevich

{"title":"Yeast Rad55-Rad57-SHU paralog complex dynamically promotes Rad51 filament formation.","authors":"Christopher W Koo, Steven K Gore, Soo Y Ro, Jie Liu, Christine Yu, Caleigh M Azumaya, Bobby Brillantes, Inna Zilberleyb, Henry Chen, Mariam B Rafiqzada, Lyra Garcia Sanchez, Wolf-Dietrich Heyer, Claudio Ciferri, Stanislau Yatskevich","doi":"10.1016/j.molcel.2026.06.045","DOIUrl":"10.1016/j.molcel.2026.06.045","url":null,"abstract":"<p><p>Homologous recombination (HR) is an important DNA repair pathway that safeguards genome integrity. During HR, the Rad51 nucleoprotein filaments catalyze strand invasion into a homologous duplex DNA. Filament formation requires a conserved family of Rad51 paralogs that act as tumor suppressors in humans. By capturing six distinct states using cryo-electron microscopy, we reveal that the Saccharomyces cerevisiae Rad51 paralog complex, composed of the Rad55-Rad57 heterodimer and the SHU (Psy3-Csm2-Shu1-Shu2) complex, selectively brings Rad51 to single-stranded DNA to seed filament formation. Rad51 itself is a transient yet integral component of this machinery which binds along the Rad57 subunit to complete a high-affinity DNA-binding site. We also uncover a dual-nucleotide regulatory mechanism: a structural ADP molecule stabilizes the complex, while a second, catalytic ATPase site at the Rad57-Rad51 interface promotes the release of the paralog complex. These structural and mechanistic features provide a blueprint for understanding the function of Rad51 paralogs across eukaryotes.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":" ","pages":"3639-3654.e13"},"PeriodicalIF":16.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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