Pub Date : 2026-01-29DOI: 10.1016/j.cell.2025.12.036
Mukesh Kumar, Christoph N. Schlaffner, Shaojun Tang, Maaike A. Beuvink, Arthur Viode, Waltraud Mair, Meenakshi Jha, Ceren Uncu, Hendrik Wesseling, Tian Wang, Derek H. Oakley, Pieter Beerepoot, Jie Xue, Theresa R. Connors, David A. Davis, Matthew P. Frosch, Melissa E. Murray, Salvatore E. Spina, Lea T. Grinberg, William W. Seeley, Bruce L. Miller, Adam L. Boxer, Daniel H. Geschwind, Kenneth S. Kosik, Dennis W. Dickson, Bernhard Y. Renard, Michael DeTure, Ann C. McKee, Bradley T. Hyman, Hanno Steen, Judith A. Steen
{"title":"Molecular features of human pathological tau distinguish tauopathy-associated dementias","authors":"Mukesh Kumar, Christoph N. Schlaffner, Shaojun Tang, Maaike A. Beuvink, Arthur Viode, Waltraud Mair, Meenakshi Jha, Ceren Uncu, Hendrik Wesseling, Tian Wang, Derek H. Oakley, Pieter Beerepoot, Jie Xue, Theresa R. Connors, David A. Davis, Matthew P. Frosch, Melissa E. Murray, Salvatore E. Spina, Lea T. Grinberg, William W. Seeley, Bruce L. Miller, Adam L. Boxer, Daniel H. Geschwind, Kenneth S. Kosik, Dennis W. Dickson, Bernhard Y. Renard, Michael DeTure, Ann C. McKee, Bradley T. Hyman, Hanno Steen, Judith A. Steen","doi":"10.1016/j.cell.2025.12.036","DOIUrl":"https://doi.org/10.1016/j.cell.2025.12.036","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"77 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072063","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}
Pub Date : 2026-01-29DOI: 10.1016/j.cell.2025.12.037
Young-Hoon Nho, Liming Qiu, Robert L. Seilheimer, Gustavo Campos, Andrew Chang, Zhengjia Wang, John F. Magnotti, Michael S. Beauchamp, Daniel A.N. Barbosa, Andreas Horn, Nolan R. Williams, Lily A. Brown, Taneeta M. Ganguly, Mario Cristancho, Bijan Pesaran, Desmond J. Oathes, Kai J. Miller, Katherine W. Scangos, Casey H. Halpern
{"title":"Human orbitofrontal neural activity is linked to obsessive-compulsive behavioral dynamics","authors":"Young-Hoon Nho, Liming Qiu, Robert L. Seilheimer, Gustavo Campos, Andrew Chang, Zhengjia Wang, John F. Magnotti, Michael S. Beauchamp, Daniel A.N. Barbosa, Andreas Horn, Nolan R. Williams, Lily A. Brown, Taneeta M. Ganguly, Mario Cristancho, Bijan Pesaran, Desmond J. Oathes, Kai J. Miller, Katherine W. Scangos, Casey H. Halpern","doi":"10.1016/j.cell.2025.12.037","DOIUrl":"https://doi.org/10.1016/j.cell.2025.12.037","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"260 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072064","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}
Pub Date : 2026-01-29DOI: 10.1016/j.cell.2025.12.049
Douglas Hanahan
{"title":"Hallmarks of cancer—Then and now, and beyond","authors":"Douglas Hanahan","doi":"10.1016/j.cell.2025.12.049","DOIUrl":"https://doi.org/10.1016/j.cell.2025.12.049","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"93 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072062","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}
Pub Date : 2026-01-28DOI: 10.1016/j.cell.2025.12.029
Gabriella N.L. Chua, Emily C. Beckwitt, Victoria Miller-Browne, Olga Yurieva, Dan Zhang, Bryce J. Katch, Nina Y. Yao, John W. Watters, Kaitlin Abrantes, Ryogo Funabiki, Xiaolan Zhao, Michael E. O’Donnell, Shixin Liu
The ring-shaped sliding clamp proliferating cell nuclear antigen (PCNA) enables DNA polymerases to perform processive DNA synthesis during replication and repair. The loading of PCNA onto DNA is catalyzed by the ATPase clamp-loader replication factor C (RFC). Using a single-molecule platform to visualize the dynamic interplay between PCNA and RFC on DNA, we unexpectedly discovered that RFC continues to associate with PCNA after loading, contrary to the conventional view. Functionally, this clamp-loader/clamp (CLC) complex is required for processive DNA synthesis by polymerase ẟ (Polẟ), as the PCNA-Polẟ assembly is inherently unstable. This architectural role of RFC is dependent on the BRCA1 C-terminal homology (BRCT) domain of Rfc1, and mutation of its DNA-binding residues causes sensitivity to genotoxic stress in vivo. We further showed that flap endonuclease I (FEN1) can also stabilize the PCNA-Polẟ interaction and mediate robust synthesis. Overall, our work revealed that, beyond their canonical enzymatic functions, PCNA-binding proteins harbor non-catalytic functions important for DNA replication and genome maintenance.
环状滑动钳增殖细胞核抗原（PCNA）使DNA聚合酶在复制和修复过程中进行DNA合成。PCNA装载到DNA上是由atp酶夹装器复制因子C （RFC）催化的。利用单分子平台可视化DNA上PCNA和RFC之间的动态相互作用，我们意外地发现RFC在加载后继续与PCNA结合，这与传统观点相反。在功能上，这种夹夹加载器/夹夹（CLC）复合体是聚合酶ẟ （Polẟ）进行DNA合成所必需的，因为PCNA-Polẟ组装本身是不稳定的。RFC的这种结构作用依赖于RFC的BRCA1 c -末端同源性（BRCT）结构域，其dna结合残基的突变导致体内对基因毒性应激的敏感性。我们进一步发现皮瓣内切酶I （FEN1）也可以稳定PCNA-Polẟ相互作用并介导稳健的合成。总的来说，我们的工作表明，除了它们典型的酶功能外，pcna结合蛋白还具有对DNA复制和基因组维持重要的非催化功能。
{"title":"A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis","authors":"Gabriella N.L. Chua, Emily C. Beckwitt, Victoria Miller-Browne, Olga Yurieva, Dan Zhang, Bryce J. Katch, Nina Y. Yao, John W. Watters, Kaitlin Abrantes, Ryogo Funabiki, Xiaolan Zhao, Michael E. O’Donnell, Shixin Liu","doi":"10.1016/j.cell.2025.12.029","DOIUrl":"https://doi.org/10.1016/j.cell.2025.12.029","url":null,"abstract":"The ring-shaped sliding clamp proliferating cell nuclear antigen (PCNA) enables DNA polymerases to perform processive DNA synthesis during replication and repair. The loading of PCNA onto DNA is catalyzed by the ATPase clamp-loader replication factor C (RFC). Using a single-molecule platform to visualize the dynamic interplay between PCNA and RFC on DNA, we unexpectedly discovered that RFC continues to associate with PCNA after loading, contrary to the conventional view. Functionally, this clamp-loader/clamp (CLC) complex is required for processive DNA synthesis by polymerase ẟ (Polẟ), as the PCNA-Polẟ assembly is inherently unstable. This architectural role of RFC is dependent on the BRCA1 C-terminal homology (BRCT) domain of Rfc1, and mutation of its DNA-binding residues causes sensitivity to genotoxic stress <em>in vivo</em>. We further showed that flap endonuclease I (FEN1) can also stabilize the PCNA-Polẟ interaction and mediate robust synthesis. Overall, our work revealed that, beyond their canonical enzymatic functions, PCNA-binding proteins harbor non-catalytic functions important for DNA replication and genome maintenance.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"78 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070585","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}
Pub Date : 2026-01-24DOI: 10.1016/j.cell.2026.01.004
Shu-Ting Hung, Gabriel R. Linares, Wen-Hsuan Chang, Yunsun Eoh, Gopinath Krishnan, Stacee Mendonca, Sarah Hong, Yingxiao Shi, Manuel Santana, Chuol Kueth, Samantha Macklin-Isquierdo, Sarah Perry, Sarah Duhaime, Claudia Maios, Jonathan Chang, Joscany Perez, Alexander Couto, Jesse Lai, Yichen Li, Samuel V. Alworth, Justin K. Ichida
(Cell 186, 786–802.e1–e15; February 16, 2023)
（Cell 186, 786-802.e1-e15； 2023年2月16日）
{"title":"PIKFYVE inhibition mitigates disease in models of diverse forms of ALS","authors":"Shu-Ting Hung, Gabriel R. Linares, Wen-Hsuan Chang, Yunsun Eoh, Gopinath Krishnan, Stacee Mendonca, Sarah Hong, Yingxiao Shi, Manuel Santana, Chuol Kueth, Samantha Macklin-Isquierdo, Sarah Perry, Sarah Duhaime, Claudia Maios, Jonathan Chang, Joscany Perez, Alexander Couto, Jesse Lai, Yichen Li, Samuel V. Alworth, Justin K. Ichida","doi":"10.1016/j.cell.2026.01.004","DOIUrl":"https://doi.org/10.1016/j.cell.2026.01.004","url":null,"abstract":"(Cell <em>186</em>, 786–802.e1–e15; February 16, 2023)","PeriodicalId":9656,"journal":{"name":"Cell","volume":"51 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042952","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}
Pub Date : 2026-01-23DOI: 10.1016/j.cell.2025.12.033
Jonathan E. Pekar, Alvin Crespo-Bellido, Philippe Lemey, Andrew S. Bowman, Thomas P. Peacock, Jennine N. Ochoa, Andrew Rambaut, Oliver G. Pybus, Michael Worobey, Martha I. Nelson
{"title":"Can H5N1 avian influenza in dairy cattle be contained in the US?","authors":"Jonathan E. Pekar, Alvin Crespo-Bellido, Philippe Lemey, Andrew S. Bowman, Thomas P. Peacock, Jennine N. Ochoa, Andrew Rambaut, Oliver G. Pybus, Michael Worobey, Martha I. Nelson","doi":"10.1016/j.cell.2025.12.033","DOIUrl":"https://doi.org/10.1016/j.cell.2025.12.033","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"119 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033203","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}
Pub Date : 2026-01-22DOI: 10.1016/j.cell.2025.12.006
Alejandro De Los Angeles, Tim Bayne, Nissim Benvenisty, Hongkui Deng, Misao Fujita, Weizhi Ji, Stephen Latham, Tianqing Li, Pentao Liu, Yuin-Han Loh, Jeantine Lunshof, Duanqing Pei, Nam Pho, José C.R. Silva, Timothy Theodore Ka Ki Tam, Tan Tao, Alan Trounson, Shao Xu, Leqian Yu, Julian Koplin, Alan Regenberg, Kiminobu Sugaya, Julian Savulescu, Magdalena Zernicka-Goetz, Robin Lovell-Badge
{"title":"A two-tier framework for responsible research on human embryo models","authors":"Alejandro De Los Angeles, Tim Bayne, Nissim Benvenisty, Hongkui Deng, Misao Fujita, Weizhi Ji, Stephen Latham, Tianqing Li, Pentao Liu, Yuin-Han Loh, Jeantine Lunshof, Duanqing Pei, Nam Pho, José C.R. Silva, Timothy Theodore Ka Ki Tam, Tan Tao, Alan Trounson, Shao Xu, Leqian Yu, Julian Koplin, Alan Regenberg, Kiminobu Sugaya, Julian Savulescu, Magdalena Zernicka-Goetz, Robin Lovell-Badge","doi":"10.1016/j.cell.2025.12.006","DOIUrl":"https://doi.org/10.1016/j.cell.2025.12.006","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"95 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033204","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}
Pub Date : 2026-01-22DOI: 10.1016/j.cell.2025.12.014
Michelle F. Griffin, Dayan J. Li, Kellen Chen, Jennifer B.L. Parker, Jason L. Guo, Seungsoo Kim, Katerina Kraft, Mauricio Downer, Annah G. Morgan, Maxwell M. Kuhnert, Serena L. Jing, Hanqi Yao, Caleb Valencia, Asha Cotterell, Michael Januszyk, Geoffrey C. Gurtner, Howard Y. Chang, Joanna Wysocka, Derrick C. Wan, Michael T. Longaker
{"title":"Fibroblasts of disparate developmental origins harbor anatomically variant scarring potential","authors":"Michelle F. Griffin, Dayan J. Li, Kellen Chen, Jennifer B.L. Parker, Jason L. Guo, Seungsoo Kim, Katerina Kraft, Mauricio Downer, Annah G. Morgan, Maxwell M. Kuhnert, Serena L. Jing, Hanqi Yao, Caleb Valencia, Asha Cotterell, Michael Januszyk, Geoffrey C. Gurtner, Howard Y. Chang, Joanna Wysocka, Derrick C. Wan, Michael T. Longaker","doi":"10.1016/j.cell.2025.12.014","DOIUrl":"https://doi.org/10.1016/j.cell.2025.12.014","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"9 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033205","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}
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