Journal ArticleDOI
Mechanisms and functions of nuclear envelope remodelling
Rosemarie Ungricht,Ulrike Kutay +1 more
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TLDR
The nuclear envelope is shown to be a dynamic and highly adaptable boundary that changes composition during differentiation, deforms in response to mechanical challenges, can be repaired upon rupture and even rapidly disassembles and reforms during open mitosis.Abstract:Â
As a compartment border, the nuclear envelope (NE) needs to serve as both a protective membrane shell for the genome and a versatile communication interface between the nucleus and the cytoplasm. Despite its important structural role in sheltering the genome, the NE is a dynamic and highly adaptable boundary that changes composition during differentiation, deforms in response to mechanical challenges, can be repaired upon rupture and even rapidly disassembles and reforms during open mitosis. NE remodelling is fundamentally involved in cell growth, division and differentiation, and if perturbed can lead to devastating diseases such as muscular dystrophies or premature ageing.read more
Citations
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Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration
Chuqian Liang,Zunpeng Liu,Moshi Song,Wei Li,Zeming Wu,Zehua Wang,Qiaoran Wang,Qiaoran Wang,Si Wang,Kaowen Yan,Liang Sun,Tomoaki Hishida,Yanning Cai,Juan Carlos Izpisua Belmonte,Pedro Guillen,Piu Chan,Qi Zhou,Weiqi Zhang,Jing Qu,Guang-Hui Liu +19 more
TL;DR: A transcription factor-independent role of CLOCK is identified in counteracting human mesenchymal stem cell decay and in stabilizing heterochromatin, promoting tissue regeneration, and mitigating aging-associated chronic diseases.
Journal ArticleDOI
Fantastic nuclear envelope herniations and where to find them.
David J Thaller,C. Patrick Lusk +1 more
TL;DR: By examining the provenance of nuclear envelope herniations associated with emerging nuclear autophagy and nuclear egress pathways, this work will provide a framework to help understand the molecular pathways that contribute to nuclear deformation.
Journal ArticleDOI
Small but mighty: the causes and consequences of micronucleus rupture
TL;DR: These consequences include a massive DNA rearrangement phenomenon called chromothripsis and activation of the cGAS-STING innate immune signaling pathway, which can be a double-edged sword with tumorigenesis and tumor prevention functions.
Journal ArticleDOI
Dynein-pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair.
Lauren Penfield,Brian Wysolmerski,Michael Mauro,Reza Farhadifar,Michael A. Q. Martinez,Ronald Biggs,Hai-Yin Wu,Curtis Broberg,Daniel J. Needleman,Shirin Bahmanyar +9 more
TL;DR: This work is the first mechanistic analysis of NE rupture and repair in an organism and indicates dynein-pulling forces enhance the severity of ruptures and lamin restricts nucleocytoplasmic mixing and allows stable NE repair.
Journal ArticleDOI
The coordination of nuclear envelope assembly and chromosome segregation in metazoans.
TL;DR: The current understanding of the coordination of NE reformation with chromosome segregation during mitotic exit in metazoans is discussed and differing models in the field are reviewed.
References
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Journal ArticleDOI
Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development
Philip J. Stephens,Christopher Greenman,Beiyuan Fu,Fengtang Yang,Graham R. Bignell,Laura Mudie,Erin Pleasance,King Wai Lau,David Beare,Lucy Stebbings,Stuart McLaren,Meng-Lay Lin,David J. McBride,Ignacio Varela,Serena Nik-Zainal,Catherine Leroy,Mingming Jia,Andrew Menzies,Adam Butler,Jon W. Teague,Michael A. Quail,John Burton,Harold Swerdlow,Nigel P. Carter,Laura Morsberger,Christine A. Iacobuzio-Donahue,George A. Follows,Anthony R. Green,Adrienne M. Flanagan,Adrienne M. Flanagan,Michael R. Stratton,P. Andrew Futreal,Peter J. Campbell,Peter J. Campbell +33 more
TL;DR: It is found that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis, which has important implications for the origins of genomic remodeling and temporal emergence of cancer.
Journal ArticleDOI
Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome
Maria Eriksson,W. Ted Brown,Leslie B. Gordon,Leslie B. Gordon,Michael W. Glynn,Joel Singer,Laura J. Scott,Michael R. Erdos,Christiane M. Robbins,Tracy Moses,Peter Berglund,Amalia Dutra,Evgenia Pak,Sandra G. Durkin,Antonei B. Csoka,Michael Boehnke,Thomas W. Glover,Francis S. Collins +17 more
TL;DR: Evidence of mutations in lamin A (LMNA) as the cause of Hutchinson–Gilford progeria syndrome is presented, and the discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.
Journal ArticleDOI
Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions
Lars Guelen,Ludo Pagie,Emilie Brasset,Wouter Meuleman,Wouter Meuleman,Marius B. Faza,Wendy Talhout,Bert H.J. Eussen,Annelies de Klein,Lodewyk F. A. Wessels,Lodewyk F. A. Wessels,Wouter de Laat,Bas van Steensel +12 more
TL;DR: A high-resolution map of the interaction sites of the entire genome with NL components in human fibroblasts is constructed and demonstrates that the human genome is divided into large, discrete domains that are units of chromosome organization within the nucleus.
Journal ArticleDOI
Nuclear lamin-A Scales With Tissue Stiffness and Enhances Matrix-Directed Differentiation
Joe Swift,Irena L. Ivanovska,Amnon Buxboim,Takamasa Harada,P.C. Dave P. Dingal,Joel Pinter,J. David Pajerowski,Kyle R. Spinler,Jae-Won Shin,Manorama Tewari,Florian Rehfeldt,David W. Speicher,Dennis E. Discher,Dennis E. Discher +13 more
TL;DR: In this article, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, as did levels of collagens in the extracellular matrix that determine E.
Journal ArticleDOI
Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Raul Mostoslavsky,Katrin F. Chua,Katrin F. Chua,David B. Lombard,Wendy W. Pang,Miriam R. Fischer,Lionel Gellon,Pingfang Liu,Gustavo Mostoslavsky,Sonia Franco,Michael M. Murphy,Kevin D. Mills,Parin Patel,Joyce T. Hsu,Andrew L. Hong,Ethan Ford,Hwei Ling Cheng,Caitlin Kennedy,Nomeli P. Nunez,Nomeli P. Nunez,Roderick T. Bronson,David Frendewey,Wojtek Auerbach,David M. Valenzuela,Margaret Karow,Michael O. Hottiger,Stephen D. Hursting,J. Carl Barrett,J. Carl Barrett,Leonard Guarente,Richard C. Mulligan,Bruce Demple,George D. Yancopoulos,Frederick W. Alt +33 more
TL;DR: It is demonstrated that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER).