Molecular Cell最新文献_第4页

A genome-scale adaptation map identifies the FANCM-RMI1/2 complex as an opposing modulator of cell fitness upon BRCA1 or BRCA2 loss 一项基因组尺度的适应图谱发现，fancm - rmi /2复合体在BRCA1或BRCA2缺失时是细胞适应性的相反调节剂

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.09.017

François Dossin,Mikael Attia,Fabricio Montero Zúñiga,Daniel González-Acosta,Rachel Brough,Fei Fei Song,Dragomir B. Krastev,Maya Raghunandan,Stephen J. Pettitt,Aurélien Boré,Amaury Vaysse,Raphaël Margueron,Massimo Lopes,Andrew N.J. Tutt,Christopher J. Lord,Ludovic Deriano

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DDIAS shields vulnerable single-stranded DNA to direct neurogenesis and protect cancer cells DDIAS保护脆弱的单链DNA来指导神经发生和保护癌细胞

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.08.026

Ashok R. Venkitaraman

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Hypoxia? NNoT a PROblem! 缺氧吗?没问题！

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.09.007

Ningning Liang,Costas A. Lyssiotis,Daniel R. Wahl

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An epigenetic program dictates MYC amplification dynamics that promote transient, extrachromosomal, and inherited genomic events 表观遗传程序决定MYC扩增动力学，促进瞬时，染色体外和遗传基因组事件

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.09.032

Benjamin I. Ferman,Chloe Azadegan,John Santoro,Anushka Udara,Madison A. Lineberger,William Lautert-Dutra,Ethan Sumner,Logan McCullough,Erin O’Donnell,Kashish Chetal,Jade Wilson,Zach Gray,Manna Ahmed,Zhijie Deng,Yan Xiong,H. Umit Kaniskan,Damayanti Chakraborty,Thomas L. Clarke,Sedona E. Murphy,Martin Walsh,Alfonso Bellacosa,Hayan Lee,Jian Jin,Capucine Van Rechem,Michael S. Lawrence,Ruslan I. Sadreyev,Johnathan R. Whetstine

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An unexpected role for cyclin E-CDK2 in regulating responses to cancer immunotherapy 细胞周期蛋白E-CDK2在调节癌症免疫治疗反应中的意外作用

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.09.005

René Bernards

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Lineage-specific innovations expand mitochondrial proteomes in kinetoplastids 谱系特异性创新扩大了着丝质体中的线粒体蛋白质组

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.08.032

Andres F. Vacas,Md Solayman,Sarah E. Calvo,Khanh Nguyen,Cameron Genxuan Lian,Keith D. Rivera,Michael Z. Chen,MitoCarta Tree of Life Consortium,Namrata D. Udeshi,Vamsi K. Mootha,Ruslan Aphasizhev,Inna Aphasizheva

{"title":"Lineage-specific innovations expand mitochondrial proteomes in kinetoplastids","authors":"Andres F. Vacas,Md Solayman,Sarah E. Calvo,Khanh Nguyen,Cameron Genxuan Lian,Keith D. Rivera,Michael Z. Chen,MitoCarta Tree of Life Consortium,Namrata D. Udeshi,Vamsi K. Mootha,Ruslan Aphasizhev,Inna Aphasizheva","doi":"10.1016/j.molcel.2026.08.032","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.08.032","url":null,"abstract":"Trypanosoma brucei and Leishmania tarentolae are model kinetoplastids whose mitochondria contain a unique DNA network, kinetoplast DNA (kDNA), and exhibit specialized features, including developmental remodeling and RNA editing. By integrating mass spectrometry-based protein correlation profiling with published datasets, we assembled inventories of 1,666 mitochondrial proteins in T. brucei and 1,594 in L. tarentolae. These include 124 polypeptides not previously recognized as mitochondrial. Despite their phylogenetic distance, trypanosomes and leishmanias maintain highly conserved mitoproteomes, including about 700 components with no detectable homologs in other eukaryotes. Comparison of T. brucei insect and mammalian stages revealed similar mitoproteome compositions but globally reduced mitochondrial protein abundance in the latter, except for components of calcium homeostasis and the alternative oxidase pathway. We also detected ten kDNA-encoded proteins, including products of pan-edited transcripts. These inventories establish a framework for functional analysis of previously uncharacterized mitochondrial factors and illuminate innovations that have shaped kinetoplastid evolution.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"17 1","pages":"4058-4074.e8"},"PeriodicalIF":16.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090152","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

Ubiquitin chain editing promotes p97/VCP-dependent removal of RPA from DNA 泛素链编辑促进p97/ vcp依赖的RPA从DNA中去除

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.09.004

Matthew Drake,Xianzhen Zhou,Alexandra McStea,Benjamin Foster,Kay Yi Chong,Martin Attwood,Leslye Roca Burgos,Laura Bennett,Sneha Anand,Merve Kaplan,Jessica J. Lu,Vaishnavi Ravikumar,Marjorie Fournier,Elena Navarro-Guerrero,Michael Ranes,Weston B. Struwe,Christopher Staples,Daniel Ebner,Ian Gibbs-Seymour

{"title":"Ubiquitin chain editing promotes p97/VCP-dependent removal of RPA from DNA","authors":"Matthew Drake,Xianzhen Zhou,Alexandra McStea,Benjamin Foster,Kay Yi Chong,Martin Attwood,Leslye Roca Burgos,Laura Bennett,Sneha Anand,Merve Kaplan,Jessica J. Lu,Vaishnavi Ravikumar,Marjorie Fournier,Elena Navarro-Guerrero,Michael Ranes,Weston B. Struwe,Christopher Staples,Daniel Ebner,Ian Gibbs-Seymour","doi":"10.1016/j.molcel.2026.09.004","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.09.004","url":null,"abstract":"DNA repair requires dynamic control of proteins on single-stranded DNA (ssDNA), yet how ubiquitin signaling regulates ssDNA-bound factors remains poorly understood. Here, we identify in human cells a ubiquitin chain-editing mechanism that promotes extraction of replication protein A (RPA) from ssDNA. We show that RPA stimulates the deubiquitinase ZUP1 and enhances its activity toward K63 linkages within ubiquitin chains. In response to DNA damage, RPA is modified with branched K48-K63 ubiquitin chains. ZUP1 selectively removes K63 linkages from these chains, remodeling the ubiquitin signal on RPA. We show that ZUP1-mediated editing of branched ubiquitin chains promotes p97/VCP-dependent removal of ubiquitinated RPA from ssDNA. Loss of ZUP1 causes accumulation of branched ubiquitin chains on RPA and pathological RPA trapping on ssDNA, resulting in elevated ssDNA signaling and genome instability. Together, our findings identify ubiquitin chain editing as a mechanism that controls RPA dynamics on ssDNA and enables p97/VCP-mediated protein extraction during DNA repair.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"9 1","pages":"3897-3914.e18"},"PeriodicalIF":16.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090154","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

Molecular glue everywhere: Metabolites join the party 到处都是分子胶，代谢物也加入其中

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.08.024

Baiyun Wang,Ning Zheng

引用次数: 0

DNASE1L3 maintains homeostatic levels of mitochondrial DNA on the mammalian cell surface DNASE1L3维持哺乳动物细胞表面线粒体DNA的稳态水平

IF 16 1区生物学

Molecular Cell Pub Date : 2026-10-01 DOI: 10.1016/j.molcel.2026.09.012

Jennifer Porat,Yizhe Sun,Valentina Poli,Stefan Petkov,Karim Almahayni,Andrew Crompton,Benson M. George,Francisca Nathália de Luna Vitorino,Li Yi,Carolina Bras Costa,Yitong Zhou,Hongxiu Wen,Latanya N. Coke,Morgane Humbel,Sandeep K. Rai,Fardin Aryan,Leon Zheng,Peter K. Gregersen,George C. Tsokos,Benjamin A. Garcia,Yixuan Xie,Suneet Agarwal,Leonhard Möckl,Ivan Zanoni,Benjamin E. Gewurz,Kim R. Simpfendorfer,Ryan A. Flynn

引用次数: 0

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