A cell cycle checkpoint for the endoplasmic reticulum

Abstract

The generation of new cells is one of the most fundamental aspects of cell biology. Proper regulation of the cell cycle is critical for human health, as underscored by many diseases associated with errors in cell cycle regulation, including both cancer and hereditary diseases. A large body of work has identified regulatory mechanisms and checkpoints that ensure accurate and timely replication and segregation of chromosomal DNA. However, few studies have evaluated the extent to which similar checkpoints exist for the division of cytoplasmic components, including organelles. Such checkpoint mechanisms might be crucial for compartments that cannot be generated de novo, such as the endoplasmic reticulum (ER). In this review, we highlight recent work in the model organism Saccharomyces cerevisiae that led to the discovery of such a checkpoint that ensures that cells inherit functional ER into the daughter cell. Evidence for cell cycle checkpoints for dividing the cytoplasmWhen a eukaryotic cell undergoes division, it faces the challenge of generating genetically identical daughter cells (Ciccia and Elledge, 2010;Matellan and Monje-Casas, 2020;Musacchio and Desai, 2017). The cell must copy the entire genome-which consists of over three billion base pairs in human-without making major mistakes. This process, called DNA replication, must occur within a specific length of time. Handling three billion base pairs alone also imposes spatial and temporal constrains to the cell. In order to ensure that the genome is separated into two dividing cells, these events are assisted by several "checkpoints" at the heart of the cell cycle operation. If mistakes are found, the cell temporally halts cell division, providing an opportunity for fixing mistakes. Upon recovery, the cell resumes the cell cycle at the point at which it stopped to finish generating a new daughter cell. The importance of cell cycle checkpoints has been underscored by many human diseases, such as cancer, that occur due to the failure of the cell to recognize or fix mistakes (Holland and Cleveland, 2012).Each year, incredible resources are poured into efforts to better understand cell cycle mechanisms and checkpoints with the hope of generating more effective treatments for cancer and other diseases.

Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System

“…Accordingly, eukaryotic cell cycle regulation integrates a huge multitude of internal and external signals to optimize survival. Failures in these processes reduce cell survival and, in higher metazoans, lead to cancer, and other diseases ( Moriel-Carretero et al, 2019 ; She et al, 2019 ; Klemm et al, 2020 ; Lai et al, 2020 ; Matellán and Monje-Casas, 2020 ; Niwa, 2020 ).…”

Sse1, Hsp110 chaperone of yeast, controls the cellular fate during Endoplasmic Reticulum-stress

“…It was previously shown that Tm-induced ER stress is known to cause cytokinesis arrest in yeast [27,28]. As sse1Δ strain continued to grow in the presence of Tmstress, it prompted us to check the cell division status of this strain following ER stress.…”

“…As sse1Δ strain showed prominent growth fitness during long-standing Tmstress and tunicamycin stress is known to cause cell division arrest in yeast [27,28], it was interesting to check the status of cell division of this deletion strain during Tm-induced ER stress. Furthermore, we found that mitotic cell cycle and cell cycle pathways to be significantly upregulated in Tm-treated sse1Δ cells by pathway enrichment analysis of the transcriptome data, as described before (Figure 5C).…”

Lung injury induces alveolar type 2 cell hypertrophy and polyploidy with implications for repair and regeneration

“…While one study suggests this may be due to excessive integrin-based extracellular matrix adhesive tension that ultimately interferes with contractility of the actin-myosin cytokinetic ring (53), there are many routes to cytokinesis failure caused by reduced or elevated Rho-signaling (54). Endoplasmic reticulum (ER)-stress itself can lead to cytokinesis failure (55, 56). Moreover, PKR, a dsRNA-dependent Protein Kinase and upstream activator of the ISR, can be activated by mitosis onset, where nuclear membrane breakdown releases endogenous dsRNAs that bind and activate PKR (57).…”