A new cell cycle checkpoint that senses plasma membrane/cell wall damage in budding yeast

Abstract

In nature, cells face a variety of stresses that cause physical damage to the plasma membrane and cell wall. It is well established that evolutionarily conserved cell cycle checkpoints monitor various cellular perturbations, including DNA damage and spindle misalignment. However, the ability of these cell cycle checkpoints to sense a damaged plasma membrane/cell wall is poorly understood. To the best of our knowledge, our recent paper described the first example of such a checkpoint, using budding yeast as a model. In this review, we will discuss this important question as well as provide hypothetical explanations to be tested in the future.

Etoposide-induced DNA damage affects multiple cellular pathways in addition to DNA damage response

“…The biological processes of GO ontology, including cellular component organization (CCO or biogen), immunological process, and metabolic process [ 41 – 44 ], are regulated by DDR. For the cellular components of GO ontology, “cell” (including cell membrane) [ 45 ], “cell part” (cellular components) [ 46 ], and “organelle” (including the nucleus, mitochondria, cytoskeleton, and others) [ 47 – 49 ] are contributors to DDR. The molecular function of GO ontology includes 1) protein interactions (“binding”) which plays an essential role in the activation of ATM, ATR, and DNAPK [ 50 , 51 ], and 2) “catalytic activity” in which a variety of posttranslational modifications are critical for DDR [ 52 , 53 ].…”

Outside‐in control – does plant cell wall integrity regulate cell cycle progression?

“…In yeast and animals, signals regulating growth and division can also derive from the yeast cell wall or the ECM. Recently, research carried out in yeast has provided mechanistic insights into the processes adapting both cell wall metabolism and composition to cell cycle progression (inside‐out control) as well as cell cycle progression to cell wall damage (CWD) impairing cell wall integrity (CWI) (outside‐in) (Kono and Ikui ). In animals, similar knowledge exists with respect to interactions between ECM and cell cycle progression (Murthy et al ), while in plants evidence regarding both inside‐out and outside‐in control is very limited.…”

Cell surface damage activates a cell cycle checkpoint (comment on DOI: 10.1002/bies.201600210)

“…These are the checkpoints that detect DNA damage (in G1 and G2 of the cell cycle) and incorrect attachment of chromosomes to the mitotic spindle in metaphase. In this issue of BioEssays , evidence is discussed by Kono and Ikui that a new G1/S‐phase checkpoint exists which monitors the status of the plasma membrane/cell wall in the budding yeast Saccharomyces cerevisiae .…”

“…Once cell surface lesions are sensed, and in addition to the induction of such repair mechanisms, recent evidence suggests that a cell cycle checkpoint is activated that prevents DNA replication . Perhaps the most important evidence described is that cells lacking the Mck1 kinase cannot activate this checkpoint in response to cell surface lesions .…”

“…The target of Mck1 seems to be the replication protein Cdc6, which is directly phosphorylated by Mck1 . Moreover, Cdc6 is degraded upon cell surface stress, and yeast with a non‐phosphorylatable mutant of Cdc6, which is resistant to degradation, cannot activate the checkpoint .…”