Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1741304
Magdalena Murawska, Andreas G Ladurner
Bromodomain AAA+ ATPases (ATPases associated with diverse cellular activities) are emerging as oncogenic proteins and compelling targets for anticancer therapies. However, structural and biochemical insight into these machines is missing. A recent study by Cho et al. reports the first cryo-EM structure of a bromodomain AAA+ ATPase and provides first insights into the functions of this putative histone chaperone.
{"title":"Bromodomain AAA+ ATPases get into shape.","authors":"Magdalena Murawska, Andreas G Ladurner","doi":"10.1080/19491034.2020.1741304","DOIUrl":"https://doi.org/10.1080/19491034.2020.1741304","url":null,"abstract":"<p><p>Bromodomain AAA+ ATPases (<u>A</u>TPases <u>a</u>ssociated with diverse cellular <u>a</u>ctivities) are emerging as oncogenic proteins and compelling targets for anticancer therapies. However, structural and biochemical insight into these machines is missing. A recent study by Cho <i>et al</i>. reports the first cryo-EM structure of a bromodomain AAA+ ATPase and provides first insights into the functions of this putative histone chaperone.</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/10.1080/19491034.2020.1741304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37753767","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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1812872
Bailey A Koch, Elizabeth Staley, Hui Jin, Hong-Guo Yu
Cellular aging occurs as a cell loses its ability to maintain homeostasis. Aging cells eliminate damaged cellular compartments and other senescence factors via self-renewal. The mechanism that regulates cellular rejuvenation remains to be further elucidated. Using budding yeast gametogenesis as a model, we show here that the endosomal sorting complex required for transport (ESCRT) III regulates nuclear envelope organization. During gametogenesis, the nuclear pore complex (NPC) and other senescence factors are sequestered away from the prospore nuclei. We show that the LEM-domain protein Heh1 (Src1) facilitates the nuclear recruitment of ESCRT-III, which is required for meiotic NPC sequestration and nuclear envelope remodeling. Furthermore, ESCRT-III-mediated nuclear reorganization appears to be critical for gamete rejuvenation, as hindering this process curtails either directly or indirectly the replicative lifespan in gametes. Our findings demonstrate the importance of ESCRT-III in nuclear envelope remodeling and its potential role in eliminating senescence factors during gametogenesis.
{"title":"The ESCRT-III complex is required for nuclear pore complex sequestration and regulates gamete replicative lifespan in budding yeast meiosis.","authors":"Bailey A Koch, Elizabeth Staley, Hui Jin, Hong-Guo Yu","doi":"10.1080/19491034.2020.1812872","DOIUrl":"https://doi.org/10.1080/19491034.2020.1812872","url":null,"abstract":"<p><p>Cellular aging occurs as a cell loses its ability to maintain homeostasis. Aging cells eliminate damaged cellular compartments and other senescence factors via self-renewal. The mechanism that regulates cellular rejuvenation remains to be further elucidated. Using budding yeast gametogenesis as a model, we show here that the endosomal sorting complex required for transport (ESCRT) III regulates nuclear envelope organization. During gametogenesis, the nuclear pore complex (NPC) and other senescence factors are sequestered away from the prospore nuclei. We show that the LEM-domain protein Heh1 (Src1) facilitates the nuclear recruitment of ESCRT-III, which is required for meiotic NPC sequestration and nuclear envelope remodeling. Furthermore, ESCRT-III-mediated nuclear reorganization appears to be critical for gamete rejuvenation, as hindering this process curtails either directly or indirectly the replicative lifespan in gametes. Our findings demonstrate the importance of ESCRT-III in nuclear envelope remodeling and its potential role in eliminating senescence factors during gametogenesis.</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/10.1080/19491034.2020.1812872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38349560","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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1815395
Yuto Takahashi, Shogo Hiratsuka, Nanako Machida, Daisuke Takahashi, Junpei Matsushita, Pavel Hozak, Tom Misteli, Kei Miyamoto, Masahiko Harata
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation of lamin A, which contributes to nuclear architecture and the spatial organization of chromatin in the nucleus. The expression of a lamin A mutant, named progerin, leads to functional and structural disruption of nuclear organization. Since progerin lacks a part of the actin-binding site of lamin A, we hypothesized that nuclear actin dynamics and function are altered in HGPS cells. Nuclear F-actin is required for the organization of nuclear shape, transcriptional regulation, DNA damage repair, and activation of Wnt/β-catenin signaling. Here we show that the expression of progerin decreases nuclear F-actin and impairs F-actin-regulated transcription. When nuclear F-actin levels are increased by overexpression of nuclear-targeted actin or by using jasplakinolide, a compound that stabilizes F-actin, the irregularity of nuclear shape and defects in gene expression can be reversed. These observations provide evidence for a novel relationship between nuclear actin and the etiology of HGPS.
{"title":"Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome.","authors":"Yuto Takahashi, Shogo Hiratsuka, Nanako Machida, Daisuke Takahashi, Junpei Matsushita, Pavel Hozak, Tom Misteli, Kei Miyamoto, Masahiko Harata","doi":"10.1080/19491034.2020.1815395","DOIUrl":"https://doi.org/10.1080/19491034.2020.1815395","url":null,"abstract":"<p><p>Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation of lamin A, which contributes to nuclear architecture and the spatial organization of chromatin in the nucleus. The expression of a lamin A mutant, named progerin, leads to functional and structural disruption of nuclear organization. Since progerin lacks a part of the actin-binding site of lamin A, we hypothesized that nuclear actin dynamics and function are altered in HGPS cells. Nuclear F-actin is required for the organization of nuclear shape, transcriptional regulation, DNA damage repair, and activation of Wnt/β-catenin signaling. Here we show that the expression of progerin decreases nuclear F-actin and impairs F-actin-regulated transcription. When nuclear F-actin levels are increased by overexpression of nuclear-targeted actin or by using jasplakinolide, a compound that stabilizes F-actin, the irregularity of nuclear shape and defects in gene expression can be reversed. These observations provide evidence for a novel relationship between nuclear actin and the etiology of HGPS.</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/10.1080/19491034.2020.1815395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38403690","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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1832734
Sunny Yang Liu, Kohta Ikegami
Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins' function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins' function in the nuclear interior.
{"title":"Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies.","authors":"Sunny Yang Liu, Kohta Ikegami","doi":"10.1080/19491034.2020.1832734","DOIUrl":"https://doi.org/10.1080/19491034.2020.1832734","url":null,"abstract":"<p><p>Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins' function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins' function in the nuclear interior.</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/10.1080/19491034.2020.1832734","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38465986","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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2019.1710329
Emma Kite, Arthur Forer
Elastic tethers, connecting telomeres of all separating anaphase chromosome pairs, lose elasticity when they lengthen during anaphase. Treatment with phosphatase inhibitor CalyculinA causes anaphase chromosomes to move backwards after they reach the poles, suggesting that dephosphorylation causes loss of tether elasticity. We added 50nM CalyculinA to living anaphase crane-fly spermatocytes with different length tethers. When tethers were short, almost all partner chromosomes moved backwards after nearing the poles. When tethers were longer, fewer chromosomes moved backwards. With yet longer tethers none moved backward. This is consistent with tether elasticity being lost by dephosphorylation. 50nM CalyculinA blocks both PP1 and PP2A. To distinguish between PP1 and PP2A we treated cells with short tethers with 50nM okadaic acid which blocks solely PP2A, or with 1µM okadaic acid which blocks both PP1 and PP2A. Only 1µM okadaic acid caused chromosomes to move backward. Thus, tether elasticity is lost because of dephosphorylation by PP1.
{"title":"The role of phosphorylation in the elasticity of the tethers that connect telomeres of separating anaphase chromosomes.","authors":"Emma Kite, Arthur Forer","doi":"10.1080/19491034.2019.1710329","DOIUrl":"https://doi.org/10.1080/19491034.2019.1710329","url":null,"abstract":"<p><p>Elastic tethers, connecting telomeres of all separating anaphase chromosome pairs, lose elasticity when they lengthen during anaphase. Treatment with phosphatase inhibitor CalyculinA causes anaphase chromosomes to move backwards after they reach the poles, suggesting that dephosphorylation causes loss of tether elasticity. We added 50nM CalyculinA to living anaphase crane-fly spermatocytes with different length tethers. When tethers were short, almost all partner chromosomes moved backwards after nearing the poles. When tethers were longer, fewer chromosomes moved backwards. With yet longer tethers none moved backward. This is consistent with tether elasticity being lost by dephosphorylation. 50nM CalyculinA blocks both PP1 and PP2A. To distinguish between PP1 and PP2A we treated cells with short tethers with 50nM okadaic acid which blocks solely PP2A, or with 1µM okadaic acid which blocks both PP1 and PP2A. Only 1µM okadaic acid caused chromosomes to move backward. Thus, tether elasticity is lost because of dephosphorylation by PP1.</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/10.1080/19491034.2019.1710329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37552009","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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1819704
Semen M Bondarenko, Igor V Sharakhov
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 usedDrosophila melanogaster LamA25 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.
{"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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1838697
David E Evans, Sarah Mermet, Christophe Tatout
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 Arabidopsis thaliana 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 Arabidopsis. 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.
{"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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1783782
Leonid A Timashev, Titia De Lange
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.
T环被认为能使端粒免受DNA损伤信号传导和DSB修复途径的影响。T环的形成需要保护蛋白成分TRF2,它能抑制ATM信号传导和NHEJ。我们在此证实,在没有其他保护蛋白的情况下,仅 TRF2 就能形成 T 环。小鼠和人类细胞含有两种 TRF2 异构体,其中一种尚未定性。我们的研究表明,这两种异构体都能保护端粒并形成t-环。这两种异构体不受细胞周期调控,t-环存在于 G1、S 和 G2 期。 我们利用DNA包裹缺陷的TRF2 Topless突变体,证实了它不能形成t环和抑制ATM。然而,由于该突变体在抑制 NHEJ 和端粒定位方面也存在缺陷,拓扑变化在端粒保护中的作用仍不清楚。 最后,我们发现 Rad51 不会影响 t 环频率或端粒保护。因此,应该探索TRF2如何形成t-环的其他模型。
{"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}
Pub Date : 2020-12-01DOI: 10.1080/19491034.2020.1742064
Shiwei Liu, David Pellman
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.
{"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}
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.
Abbreviations: 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.
核膜将真核细胞中的染色质分隔开来。核膜的主要成分是片层蛋白,它们与包括 LEM 结构域蛋白在内的一系列因子结合在一起。哺乳动物细胞的核膜在细胞分裂过程中打开。在有丝分裂末期,当端粒拴在核外围时,核包膜重新组装并与染色质结合。Lamins、LEM结构域蛋白和DNA结合因子(如BAF)有助于染色质的重组。在这一背景下,ESCRT 复合物的作用正在崭露头角,它是一种在多种膜组装途径(包括核包膜重组)中发挥作用的机制。这一领域的研究正在揭示ESCRT如何从机制上与作为LEM结构域蛋白的核包膜相关因子联系起来。重要的是,ESCRTs 还能在间期修复核包膜破裂。总之,这一领域的研究进展为解释与核包膜脆性有关的疾病(如层状细胞病和癌症)提供了新的线索。缩写:NE,核膜;LEM,LAP2-emerin-MAN1(LEM)-domain containing proteins;LINC,linker of nucleoskeleton and cytoskeleton complexes;Cyt,cytoplasm;Chr,染色质;MB,中体;End,内体;Tel,端粒;INM,核内膜;NP,核质;NPC,核孔复合体;ER,内质网;SPB,纺锤极体。
{"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}