scholarly journals Meiotic Cellular Rejuvenation is Coupled to Nuclear Remodeling in Budding Yeast

2019 ◽  
Author(s):  
Grant A. King ◽  
Jay S. Goodman ◽  
Keerthana Chetlapalli ◽  
Jennifer G. Schick ◽  
Danielle M. Jorgens ◽  
...  
Keyword(s):  
Quality Control ◽  
De Novo ◽  
Budding Yeast ◽  
Time Lapse ◽  
Cellular Damage ◽  
Nuclear Pore ◽  
The Core ◽  
Nucleolar Material ◽  
Nuclear Remodeling ◽  
Insight Into

ABSTRACTProduction of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents. Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism. Using time-lapse fluorescence microscopy in budding yeast, we found that nuclear senescence factors – including protein aggregates, extrachromosomal ribosomal DNA circles, and abnormal nucleolar material – are sequestered away from chromosomes during meiosis II and subsequently eliminated. A similar sequestration and elimination process occurs for the core subunits of the nuclear pore complex in both young and old cells. Nuclear envelope remodeling drives the formation of a membranous compartment containing the sequestered material. Importantly,de novogeneration of plasma membrane is required for the sequestration event, preventing the inheritance of long-lived nucleoporins and senescence factors into the newly formed gametes. Our study uncovers a new mechanism of nuclear quality control and provides insight into its function in meiotic cellular rejuvenation.

scholarly journals Meiotic cellular rejuvenation is coupled to nuclear remodeling in budding yeast

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Grant A King ◽  
Jay S Goodman ◽  
Jennifer G Schick ◽  
Keerthana Chetlapalli ◽  
Danielle M Jorgens ◽  
...  
Keyword(s):  
Quality Control ◽  
De Novo ◽  
Budding Yeast ◽  
Time Lapse ◽  
Cellular Damage ◽  
Nuclear Pore ◽  
The Core ◽  
Nucleolar Material ◽  
Nuclear Remodeling ◽  
Insight Into

Production of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents. Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism. Using time-lapse fluorescence microscopy in budding yeast, we found that nuclear senescence factors – including protein aggregates, extrachromosomal ribosomal DNA circles, and abnormal nucleolar material – are sequestered away from chromosomes during meiosis II and subsequently eliminated. A similar sequestration and elimination process occurs for the core subunits of the nuclear pore complex in both young and aged cells. Nuclear envelope remodeling drives the formation of a membranous compartment containing the sequestered material. Importantly, de novo generation of plasma membrane is required for the sequestration event, preventing the inheritance of long-lived nucleoporins and senescence factors into the newly formed gametes. Our study uncovers a new mechanism of nuclear quality control and provides insight into its function in meiotic cellular rejuvenation.

scholarly journals Autophagosome biogenesis: From membrane growth to closure

2020 ◽  
Vol 219 (6) ◽  
Author(s):  
Thomas J. Melia ◽  
Alf H. Lystad ◽  
Anne Simonsen
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Membrane Vesicle ◽  
Double Membrane ◽  
The Core ◽  
Membrane Modeling ◽  
Membrane Growth ◽  
Initial Discovery ◽  
Insight Into ◽  
Key Questions

Autophagosome biogenesis involves de novo formation of a membrane that elongates to sequester cytoplasmic cargo and closes to form a double-membrane vesicle (an autophagosome). This process has remained enigmatic since its initial discovery >50 yr ago, but our understanding of the mechanisms involved in autophagosome biogenesis has increased substantially during the last 20 yr. Several key questions do remain open, however, including, What determines the site of autophagosome nucleation? What is the origin and lipid composition of the autophagosome membrane? How is cargo sequestration regulated under nonselective and selective types of autophagy? This review provides key insight into the core molecular mechanisms underlying autophagosome biogenesis, with a specific emphasis on membrane modeling events, and highlights recent conceptual advances in the field.

scholarly journals Flexibly-oriented double Cdc45-MCM-GINS intermediates during eukaryotic replicative helicase maturation

2018 ◽  
Author(s):  
Lu Liu ◽  
Yue Zhang ◽  
Jingjing Zhang ◽  
Jian-Hua Wang ◽  
Qinhong Cao ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Quality Control ◽  
Mass Spectra ◽  
De Novo ◽  
S Phase ◽  
Replicative Helicase ◽  
The Core ◽  
Origin Activation ◽  
Bona Fide ◽  
Phase Proceeds

AbstractThe core of the eukaryotic helicase MCM is loaded as an inactive double hexamer (DH). How it is assembled into two active Cdc45-MCM-GINS (CMG) helicases remains elusive. Here, we report that at the onset of S phase, both Cdc45 and GINS are loaded as dimers onto MCM DH, resulting in formation of double CMG (d-CMG). As S phase proceeds, d-CMGs gradually mature into two single CMG-centered replisome progression complexes (RPCs). Mass spectra reveal that RPA and DNA Pol α/primase co-purify exclusively with RPCs, but not with d-CMGs. Consistently, d-CMGs are not able to catalyze either the unwinding or de novo DNA synthesis, while RPCs can do both. Using single-particle electron microscopy, we have obtained 2D class averages of d-CMGs. Compared to MCM DHs, they display heterogeneous, flexibly orientated and partially loosened conformations with changed interfaces. The dumbbell-shaped d-CMGs are mediated by Ctf4, while other types of d-CMGs are independent of Ctf4. These data suggest CMG dimers as bona fide intermediates during MCM maturation, providing an additional quality control for symmetric origin activation and bidirectional replication.

scholarly journals Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis

Structure ◽  
2017 ◽  
Vol 25 (6) ◽  
pp. 912-923.e5 ◽  
Author(s):  
María Moreno-Morcillo ◽  
Araceli Grande-García ◽  
Alba Ruiz-Ramos ◽  
Francisco del Caño-Ochoa ◽  
Jasminka Boskovic ◽  
...  
Keyword(s):  
De Novo ◽  
Pyrimidine Biosynthesis ◽  
Multifunctional Protein ◽  
The Core ◽  
Structural Insight ◽  
Insight Into

Will Love Tear Us Apart: Adapting the Lyrical to the Ludic

CounterText ◽  
2016 ◽  
Vol 2 (2) ◽  
pp. 217-235
Author(s):  
Gordon Calleja
Keyword(s):  
Design Process ◽  
Game Design ◽  
Digital Games ◽  
Design Decisions ◽  
The Core ◽  
Lyrical Poetry ◽  
Insight Into ◽  
Made In

This paper gives an insight into the design process of a game adaptation of Joy Division's Love Will Tear Us Apart (1980). It outlines the challenges faced in attempting to reconcile the diverging qualities of lyrical poetry and digital games. In so doing, the paper examines the design decisions made in every segment of the game with a particular focus on the tension between the core concerns of the lyrical work being adapted and established tenets of game design.

Force in Nature

2020 ◽  
pp. 146-160
Author(s):  
David Carus
Keyword(s):  
Natural Science ◽  
The Body ◽  
The Core ◽  
Thing In Itself ◽  
The Will ◽  
Insight Into

This chapter explores Schopenhauer’s concept of force, which lies at the root of his philosophy. It is force in nature and thus in natural science that is inexplicable and grabs Schopenhauer’s attention. To answer the question of what this inexplicable term is at the root of all causation, Schopenhauer looks to the will within us. Through will, he maintains that we gain immediate insight into forces in nature and hence into the thing in itself at the core of everything and all things. Will is thus Schopenhauer’s attempt to answer the question of the essence of appearance. Yet will, as it turns out, cannot be known immediately as it is subject to time, and the acts of will, which we experience within us, do not correlate immediately with the actions of the body (as Schopenhauer had originally postulated). Hence, the acts of will do not lead to an explanation of force, which is at the root of causation in nature. Schopenhauer sets out to explain what is at the root of all appearances, derived from the question of an original cause, or as Schopenhauer states “the cause of causation,” but cannot determine this essence other than by stating that it is will; a will, however, that cannot be immediately known.

scholarly journals Neurofilament Proteolysis after Focal Ischemia; When Do Cells Die after Experimental Stroke?

1999 ◽  
Vol 19 (6) ◽  
pp. 652-660 ◽  
Author(s):  
Jaroslaw Aronowski ◽  
Ki-Hyun Cho ◽  
Roger Strong ◽  
James C. Grotta
Keyword(s):  
Time Course ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Cellular Damage ◽  
Experimental Stroke ◽  
Infarct Core ◽  
Similar Time ◽  
The Core ◽  
Tetrazolium Staining ◽  
Previous Demonstration

To determine the occurrence and time-course of presumably irreversible subcellular damage after moderate focal ischemia, rats were subjected to 1, 3, 6, 9, or 24 hours of permanent unilateral middle cerebral and common carotid occlusion or 3 hours of reversible occlusion followed by 3, 6, or 21 hours of reperfusion. The topography and the extent of damage were analyzed with tetrazolium staining and immunoblot using an antibody capable of detecting breakdown of neurofilament. Neurofilament proteolysis began after 3 hours in the infarct core but was still incomplete in penumbral regions up to 9 hours. Similarly, tetrazolium-staining abnormalities were observed in the core of 50% of animals after 3 hours of ischemia. At 6 hours of permanent ischemia, infarct volume was maximal, and further prolongation of occlusion to 9 or 24 hours did not increase abnormal tetrazolium staining. In contrast to permanent ischemia and in agreement with the authors' previous demonstration of “reperfusion injury” in this model, prolongation of reperfusion from 3 hours to 6 and 21 hours after 3 hours of reversible occlusion gradually augmented infarct volume by 203% and 324%, respectively. Neurofilament proteolysis initiated approximately 3 hours after ischemia was quantitatively greatest in the core and extended during reperfusion to incorporate penumbra with a similar time course to that of tetrazolium abnormalities. These data demonstrate that, at least as measured by neurofilament breakdown and mitochondrial failure, extensive cellular damage is not present in penumbral regions for up to 9 hours, suggesting the potential for rescuing these regions by appropriate and timely neuroprotective strategies.

Sign in / Sign up

Export Citation Format

Share Document