Transfer of the Septin Ring to Cytokinetic Remnants in ER Stress Directs Age-Sensitive Cell-Cycle Re-entry

Regulation of the early stages of endoplasmic reticulum inheritance during ER stress

“…Two yeast-two hybrid screens have demonstrated that Spa2 interacts directly with Slt2 (Sheu et al, 1998;van Drogen and Peter, 2002; Supplemental Figure S2B). Importantly, while reexamining our previously published DHFR screen for Slt2 (Chao et al, 2019), we noticed that Spa2 showed increased interactions with Slt2 during ER stress (Supplemental Figure S2C). In addition to these physical interaction data, other lines of evidence also suggest that Spa2 may function with Slt2 in ER inheritance under normal growth conditions (Loewen et al, 2007;Li et al, 2013).…”

“…Previously, we reported that the MAP kinase Slt2 is needed for activating the ERSU pathway (Babour et al, 2010). While Slt2 performs multiple cellular functions, we found that the population of Slt2 involved in ERSU is localized to the bud tip (Chao et al, 2019). Thus, we reasoned that identifying Slt2 interacting partners at the bud tip might be an avenue to uncover the component(s) that anchors the IET at the bud tip.…”

“…We reported that ER stress inhibits cER inheritance into the daughter cell as part of the ERSU events (Babour et al, 2010;Piña and Niwa, 2015;Piña et al, 2016Piña et al, , 2018Chao et al, 2019). Although ER inheritance during normal growth conditions has been described, ER inheritance during ER stress has not been investigated in detail.…”

“…Previously, we discovered a cell-cycle checkpoint mechanism called the ER stress surveillance (ERSU) pathway that ensures that daughter cells inherit functional ER, and not ER that has been damaged by ER stress (Babour et al, 2010). Ultimately, the blocking of ER inheritance during ER stress leads to the cytokinesis block, leading to the halting of the cell cycle (Chao et al, 2019). Interestingly, we found that the ERSU pathway is independent of the well-known unfolded protein response (UPR) pathway (Walter and Ron, 2011) that reestablishes ER homeostasis.…”

A cell cycle checkpoint for the endoplasmic reticulum

“…In recent years, studies have begun to unravel the molecular mechanisms that ensure the inheritance of functional ER to a daughter cell. Here, we provide an overview of an exciting discovery of a cell cycle regulatory checkpoint-termed the ER stress surveillance (ERSU) cell cycle checkpoint-in the budding yeast Saccharomyces cerevisiae (S. cerevisiae) (Babour et al, 2010;Chao et al, 2019;Pina et al, 2018;Pina et al, 2016;Pina and Niwa, 2015). Since the initial discovery of the ERSU pathway, subsequent work has provided intriguing mechanistic insights on the ERSU cell cycle checkpoint.…”