The coordination of nuclear envelope assembly and chromosome segregation in metazoans

Liu, Shiwei; Pellman, David

doi:10.1080/19491034.2020.1742064

Cited by 53 publications

(80 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7c, d ). Downregulated cell cycle genes such as Cdk1 and Aurkb control nuclear envelope assembly and disassembly by regulating chromosomal condensation 30 , whereas kinesins ( Kif4 , Kif22 ) have been shown to be required in the muscle for nuclear positioning 31 . We observed alterations in the expression of myosin heavy chain genes and key sarcomeric components, including myozenin-1, myosin-binding protein C, myosin light chain 1, and tropomyosin 1 (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization

et al. 2021

View full text Add to dashboard Cite

Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism. These abnormalities resemble those of Emery–Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.

show abstract

Section: Resultsmentioning

confidence: 99%

The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In addition to differences in their mitotic localization, nuclear envelope components are categorized by their localization on decondensing chromatin surfaces following chromosome segregation (Clever et al, 2013; Liu and Pellman, 2019). Lamin A/C, a nuclear envelope protein found ubiquitously throughout the cytoplasm during mitosis, is a “core” nuclear envelope component, as it is recruited to the central chromosome mass nearest the central spindle axis during nuclear envelope reformation (Clever et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

“…Alternatively, lamin B is a “non-core” component because it is targeted to the chromosome peripheral regions during nuclear envelope reformation (Clever et al, 2013). Incorporation of non-core components is necessary for transport-competent nuclear envelopes and proper nuclear functions (Hetzer, 2010; Clever et al, 2013, Liu and Pellman, 2019). Micronuclear envelope stability is enhanced by successful recruitment of lamin B, while loss of lamin B causes holes to form in the lamina, increasing the frequency of nuclear envelope rupture (Vergnes et al, 2004; Vargas et al, 2012; Hatch et al, 2013; Liu et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Micronuclei arising due to loss of KIF18A form stable micronuclear envelopes and do not promote tumorigenesis

Martin

et al. 2020

Preprint

View full text Add to dashboard Cite

Micronuclei, whole or fragmented chromosomes which are spatially separated from the main nucleus, are strongly associated with genomic instability and have been identified as drivers of tumorigenesis. Paradoxically, Kif18a mutant mice produce micronuclei due to unaligned chromosomes in vivo but do not develop spontaneous tumors, raising questions about whether all micronuclei contribute similarly to genomic instability and cancer. We report here that micronuclei in Kif18a mutant mice form stable nuclear envelopes. Challenging Kif18a mutant mice via deletion of the Trp53 gene led to formation of thymic lymphoma with elevated levels of micronuclei. However, loss of Kif18a had modest or no effect on survival of Trp53 homozygotes and heterozygotes, respectively. To further explore micronuclear envelope stability in KIF18A KO cells, we compared micronuclei induced via different insults in cultured cells. Micronuclei in KIF18A KO cells form stable nuclear envelopes characterized by increased recruitment of core and non-core nuclear envelope components and successful expansion of decondensing chromatin compared to those induced by microtubule drug washout or exposure to radiation. We also observed that lagging chromosomes, which lead to micronucleus formation, were positioned closer to the main chromatin masses, and further from the central spindle, in KIF18A KO cells. Our studies provide in vivo support to models suggesting that micronuclear fate depends on the sub-cellular location of late lagging chromosomes and suggest that not all micronuclei actively promote tumorigenesis.

show abstract

“…This defect may by a consequence of incorrect chromosome segregation induced by different chromosome rearrangements (mostly translocations) [ 41 ]. On the other hand, segregation errors lead to discoordination in the reformation of the nuclear envelope [ 42 ]. Indeed, we observed Lamin-negative nuclei in Trf2 depleted cells ( Figure 6 ) which indicates a problem with nuclear envelope reformation in cells with decreased Trf2 expression.…”

Section: Discussionmentioning

confidence: 99%

TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation

Cherezov

Vorontsova

Симонова

2020

IJMS

View full text Add to dashboard Cite

Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. TBP-related factor 2 (Trf2) encodes an alternative general transcription factor. A decrease of TRF2 expression disrupts the structure of the pericentromeric regions and prevents their association into chromocenter. We revealed several centric fusions in two lines of Drosophila melanogaster with weak Trf2 alleles in genetic experiments. We performed an RNAi-mediated knock-down of Trf2 in Drosophila and S2 cells and demonstrated that Trf2 upregulates expression of D1—one of the major genes responsible for chromocenter formation and nuclear integrity in Drosophila. Our data, for the first time, indicate that Trf2 may be involved in transcription program responsible for structuring of pericentromeric regions and may contribute to new karyotypes formation in particular by promoting centric fusion. Insight into the molecular mechanisms of Trf2 function and its new targets in different tissues will contribute to our understanding of its phenomenon.

show abstract

The coordination of nuclear envelope assembly and chromosome segregation in metazoans

Cited by 53 publications

References 134 publications

The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization

The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization

Micronuclei arising due to loss of KIF18A form stable micronuclear envelopes and do not promote tumorigenesis

TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation

Contact Info

Product

Resources

About