{"title":"Reorganization of the nuclear architecture in the <i>Drosophila melanogaster</i> Lamin B mutant lacking the CaaX box.","authors":"Semen M Bondarenko, Igor V Sharakhov","doi":"10.1080/19491034.2020.1819704","DOIUrl":"https://doi.org/10.1080/19491034.2020.1819704","url":null,"abstract":"<p><p>Lamins interact with the nuclear membrane and chromatin but the precise players and mechanisms of these interactions are unknown. Here, we tested whether the removal of the CaaX motif from Lamin B disrupts its attachment to the nuclear membrane and affects chromatin distribution. We used<i>Drosophila melanogaster Lam<sup>A25</sup></i> homozygous mutants that lack the CaaX box. We found that the mutant Lamin B was not confined to the nuclear periphery but was distributed throughout the nuclear interior, colocalizing with chromosomes in salivary gland and proventriculus. The peripheral position of Lamin C, nuclear pore complex (NPC), heterochromatin protein 1a (HP1a), H3K9me2- and H3K27me3-associated chromatin remained intact. The fluorescence intensity of the DAPI-stained peripheral chromatin significantly decreased and that of the central chromatin significantly increased in the proventriculus nuclei of the mutantflies compared to wild-type. However, the mutation had little effect on chromatin radial distribution inside highly polytenized salivary gland nuclei.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1819704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38405789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing knowledge of the plant nuclear periphery and its application for crop science.","authors":"David E Evans, Sarah Mermet, Christophe Tatout","doi":"10.1080/19491034.2020.1838697","DOIUrl":"https://doi.org/10.1080/19491034.2020.1838697","url":null,"abstract":"<p><p>In this review, we explore recent advances in knowledge of the structure and dynamics of the plant nuclear envelope. As a paradigm, we focused our attention on the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, a structurally conserved bridging complex comprising SUN domain proteins in the inner nuclear membrane and KASH domain proteins in the outer nuclear membrane. Studies have revealed that this bridging complex has multiple functions with structural roles in positioning the nucleus within the cell, conveying signals across the membrane and organizing chromatin in the 3D nuclear space with impact on gene transcription. We also provide an up-to-date survey in nuclear dynamics research achieved so far in the model plant <i>Arabidopsis thaliana</i> that highlights its potential impact on several key plant functions such as growth, seed maturation and germination, reproduction and response to biotic and abiotic stress. Finally, we bring evidences that most of the constituents of the LINC Complex and associated components are, with some specificities, conserved in monocot and dicot crop species and are displaying very similar functions to those described for <i>Arabidopsis</i>. This leads us to suggest that a better knowledge of this system and a better account of its potential applications will in the future enhance the resilience and productivity of crop plants.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1838697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38691601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of t-loop formation by TRF2.","authors":"Leonid A Timashev, Titia De Lange","doi":"10.1080/19491034.2020.1783782","DOIUrl":"10.1080/19491034.2020.1783782","url":null,"abstract":"<p><p>T-loops are thought to hide telomeres from DNA damage signaling and DSB repair pathways. T-loop formation requires the shelterin component TRF2, which represses ATM signaling and NHEJ. Here we establish that TRF2 alone, in the absence of other shelterin proteins can form t-loops. Mouse and human cells contain two isoforms of TRF2, one of which is uncharacterized. We show that both isoforms protect telomeres and form t-loops. The isoforms are not cell cycle regulated and t-loops are present in G1, S, and G2. Using the DNA wrapping deficient TRF2 Topless mutant, we confirm its inability to form t-loops and repress ATM. However, since the mutant is also defective in repression of NHEJ and telomeric localization, the role of topological changes in telomere protection remains unclear. Finally, we show that Rad51 does not affect t-loop frequencies or telomere protection. Therefore, alternative models for how TRF2 forms t-loops should be explored.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38066880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interplay of the nuclear envelope with chromatin in physiology and pathology.","authors":"Romina Burla, Mattia La Torre, Klizia Maccaroni, Fiammetta Verni, Simona Giunta, Isabella Saggio","doi":"10.1080/19491034.2020.1806661","DOIUrl":"10.1080/19491034.2020.1806661","url":null,"abstract":"<p><p>The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain proteins. The nuclear envelope of mammalian cells opens up during cell division. It is reassembled and associated with chromatin at the end of mitosis when telomeres tether to the nuclear periphery. Lamins, LEM domain proteins, and DNA binding factors, as BAF, contribute to the reorganization of chromatin. In this context, an emerging role is that of the ESCRT complex, a machinery operating in multiple membrane assembly pathways, including nuclear envelope reformation. Research in this area is unraveling how, mechanistically, ESCRTs link to nuclear envelope associated factors as LEM domain proteins. Importantly, ESCRTs work also during interphase for repairing nuclear envelope ruptures. Altogether the advances in this field are giving new clues for the interpretation of diseases implicating nuclear envelope fragility, as laminopathies and cancer.</p><p><strong>Abbreviations: </strong>na, not analyzed; ko, knockout; kd, knockdown; NE, nuclear envelope; LEM, LAP2-emerin-MAN1 (LEM)-domain containing proteins; LINC, linker of nucleoskeleton and cytoskeleton complexes; Cyt, cytoplasm; Chr, chromatin; MB, midbody; End, endosomes; Tel, telomeres; INM, inner nuclear membrane; NP, nucleoplasm; NPC, Nuclear Pore Complex; ER, Endoplasmic Reticulum; SPB, spindle pole body.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/93/KNCL_11_1806661.PMC7529417.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38301825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The coordination of nuclear envelope assembly and chromosome segregation in metazoans.","authors":"Shiwei Liu, David Pellman","doi":"10.1080/19491034.2020.1742064","DOIUrl":"10.1080/19491034.2020.1742064","url":null,"abstract":"<p><p>The nuclear envelope (NE) is composed of two lipid bilayer membranes that enclose the eukaryotic genome. In interphase, the NE is perforated by thousands of nuclear pore complexes (NPCs), which allow transport in and out of the nucleus. During mitosis in metazoans, the NE is broken down and then reassembled in a manner that enables proper chromosome segregation and the formation of a single nucleus in each daughter cell. Defects in coordinating NE reformation and chromosome segregation can cause aberrant nuclear architecture. This includes the formation of micronuclei, which can trigger a catastrophic mutational process commonly observed in cancers called chromothripsis. Here, we discuss the current understanding of the coordination of NE reformation with chromosome segregation during mitotic exit in metazoans. We review differing models in the field and highlight recent work suggesting that normal NE reformation and chromosome segregation are physically linked through the timing of mitotic spindle disassembly.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37768740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew S Nord, Cyril Bernis, Sarah Carmona, Dennis C Garland, Anna Travesa, Douglass J Forbes
{"title":"Exportins can inhibit major mitotic assembly events <i>in vitro</i>: membrane fusion, nuclear pore formation, and spindle assembly.","authors":"Matthew S Nord, Cyril Bernis, Sarah Carmona, Dennis C Garland, Anna Travesa, Douglass J Forbes","doi":"10.1080/19491034.2020.1798093","DOIUrl":"https://doi.org/10.1080/19491034.2020.1798093","url":null,"abstract":"<p><strong>Xenopus: </strong>egg extracts are a powerful <i>in vitro</i> tool for studying complex biological processes, including nuclear reconstitution, nuclear membrane and pore assembly, and spindle assembly. Extracts have been further used to demonstrate a moonlighting regulatory role for nuclear import receptors or <i>importins</i> on these cell cycle assembly events. Here we show that <i>exportins</i> can also play a role in these events. Addition of Crm1, Exportin-t, or Exportin-5 decreased nuclear pore assembly in vitro. RanQ69L-GTP, a constitutively active form of RanGTP, ameliorated inhibition. Both Crm1 and Exportin-t inhibited fusion of nuclear membranes, again counteracted by RanQ69L-GTP. In mitotic extracts, Crm1 and Exportin-t negatively impacted spindle assembly. Pulldowns from the extracts using Crm1- or Exportin-t-beads revealed nucleoporins known to be essential for both nuclear pore and spindle assembly, with RanQ69L-GTP decreasing a subset of these target interactions. This study suggests a model where exportins, like importins, can regulate major mitotic assembly events.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1798093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38245606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SATB1-mediated chromatin landscape in T cells.","authors":"Tomas Zelenka, Charalampos Spilianakis","doi":"10.1080/19491034.2020.1775037","DOIUrl":"https://doi.org/10.1080/19491034.2020.1775037","url":null,"abstract":"<p><p>The regulatory circuits that define developmental decisions of thymocytes are still incompletely resolved. SATB1 protein is predominantly expressed at the CD4<sup>+</sup>CD8<sup>+</sup>cell stage exerting its broad transcription regulation potential with both activatory and repressive roles. A series of post-translational modifications and the presence of potential SATB1 protein isoforms indicate the complexity of its regulatory potential. The most apparent mechanism of its involvement in gene expression regulation is via the orchestration of long-range chromatin loops between genes and their regulatory elements. Multiple SATB1 perturbations in mice uncovered a link to autoimmune diseases while clinical investigations on cancer research uncovered that SATB1 has a promoting role in several types of cancer and can be used as a prognostic biomarker. SATB1 is a multivalent tissue-specific factor with a broad and yet undetermined regulatory potential. Future investigations on this protein could further uncover T cell-specific regulatory pathways and link them to (patho)physiology.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1775037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39094184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalie Y Chen, Paul H Kim, Loren G Fong, Stephen G Young
{"title":"Nuclear membrane ruptures, cell death, and tissue damage in the setting of nuclear lamin deficiencies.","authors":"Natalie Y Chen, Paul H Kim, Loren G Fong, Stephen G Young","doi":"10.1080/19491034.2020.1815410","DOIUrl":"10.1080/19491034.2020.1815410","url":null,"abstract":"<p><p>The nuclear membranes function as a barrier to separate the cell nucleus from the cytoplasm, but this barrier can be compromised by nuclear membrane ruptures, leading to intermixing of nuclear and cytoplasmic contents. Spontaneous nuclear membrane ruptures (<i>i.e</i>., ruptures occurring in the absence of mechanical stress) have been observed in cultured cells, but they are more frequent in the setting of defects or deficiencies in nuclear lamins and when cells are subjected to mechanical stress. Nuclear membrane ruptures in cultured cells have been linked to DNA damage, but the relevance of ruptures to developmental or physiologic processes <i>in vivo</i> has received little attention. Recently, we addressed that issue by examining neuronal migration in the cerebral cortex, a developmental process that subjects the cell nucleus to mechanical stress. In the setting of lamin B1 deficiency, we observed frequent nuclear membrane ruptures in migrating neurons in the developing cerebral cortex and showed that those ruptures are likely the cause of observed DNA damage, neuronal cell death, and profound neuropathology. In this review, we discuss the physiologic relevance of nuclear membrane ruptures, with a focus on migrating neurons in cell culture and in the cerebral cortex of genetically modified mice.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1815410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38365679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin Xie, S Raza Mahmood, Tamara Gjorgjieva, Piergiorgio Percipalle
{"title":"Emerging roles of cytoskeletal proteins in regulating gene expression and genome organization during differentiation.","authors":"Xin Xie, S Raza Mahmood, Tamara Gjorgjieva, Piergiorgio Percipalle","doi":"10.1080/19491034.2020.1742066","DOIUrl":"https://doi.org/10.1080/19491034.2020.1742066","url":null,"abstract":"<p><p>In the eukaryotic cell nucleus, cytoskeletal proteins are emerging as essential players in nuclear function. In particular, actin regulates chromatin as part of ATP-dependent chromatin remodeling complexes, it modulates transcription and it is incorporated into nascent ribonucleoprotein complexes, accompanying them from the site of transcription to polyribosomes. The nuclear actin pool is undistinguishable from the cytoplasmic one in terms of its ability to undergo polymerization and it has also been implicated in the dynamics of chromatin, regulating heterochromatin segregation at the nuclear lamina and maintaining heterochromatin levels in the nuclear interiors. One of the next frontiers is, therefore, to determine a possible involvement of nuclear actin in the functional architecture of the cell nucleus by regulating the hierarchical organization of chromatin and, thus, genome organization. Here, we discuss the repertoire of these potential actin functions and how they are likely to play a role in the context of cellular differentiation.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1742066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37771241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuclear filaments: role in chromosomal positioning and gene expression.","authors":"Manindra Bera, Kaushik Sengupta","doi":"10.1080/19491034.2020.1769445","DOIUrl":"https://doi.org/10.1080/19491034.2020.1769445","url":null,"abstract":"ABSTRACT Nuclear lamins form an elastic meshwork underlying the inner nuclear membrane and provide mechanical rigidity to the nucleus and maintain shape. Lamins also maintain chromosome positioning and play important roles in several nuclear processes like replication, DNA damage repair, transcription, and epigenetic modifications. LMNA mutations affect cardiac tissue, muscle tissues, adipose tissues to precipitate several diseases collectively termed as laminopathies. However, the rationale behind LMNA mutations and laminopathies continues to elude scientists. During interphase, several chromosomes form inter/intrachromosomal contacts inside nucleoplasm and several chromosomal loops also stretch out to make a ‘loop-cluster’ which are key players to regulate gene expressions. In this perspective, we have proposed that the lamin network in tandem with nuclear actin and myosin provide mechanical rigidity to the chromosomal contacts and facilitate loop-clusters movements. LMNA mutations thus might perturb the landscape of chromosomal contacts or loop-clusters positioning which can impair gene expression profile.","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1769445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37976523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}