TORC1 regulates the DNA damage checkpoint via checkpoint protein levels

Miyamoto, Ikuko; Ozaki, Ryota; Yamaguchi, Kazuyuki; Yamamoto, Kaori; Kaneko, Atsuki; Ushimaru, Takashi

doi:10.1016/j.bbrc.2019.02.010

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…Nonetheless, these studies illustrate that the DNA damage response requires an active growth signaling response [139]. Recent data also suggests that TORC1 inhibition results in lower levels of checkpoint proteins [157]. Thus, it may appear that TORC1 may be required for both checkpoint activation and for adaptation.…”

Section: Nutrient Sensing and The Regulation Of Adaptation And The Checkpoint Responsementioning

confidence: 88%

Checkpoint Control of DNA Repair in Yeast

Fasullo¹

2021

Saccharomyces

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Budding yeast has been a model organism for understanding how DNA damage is repaired and how cells minimize genetic instability caused by arresting or delaying the cell cycle at well-defined checkpoints. However, many DNA damage insults are tolerated by mechanisms that can both be error-prone and error-free. The mechanisms that tolerate DNA damage and promote cell division are less well-understood. This review summarizes current information known about the checkpoint response to agents that elicit both the G2/M checkpoint and the intra-S phase checkpoint and how cells adapt to unrepaired DNA damage. Tolerance to particular bulky DNA adducts and radiomimetic agents are discussed, as well as possible mechanisms that may control phosphatases that deactivate phosphorylated proteins.

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Section: Nutrient Sensing and The Regulation Of Adaptation And The Checkpoint Responsementioning

confidence: 88%

Checkpoint Control of DNA Repair in Yeast

Fasullo¹

2021

Saccharomyces

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“…One interesting question concerns how, the regulation of Cdc25 activity, phosphorylation and ubiquitin-dependent degradation of Cdc25 activity is integrated [23][24][25]. Given that cross talk occurs between the TORC1, DDR and ESR pathways [26][27][28], understanding how caffeine modulates Cdc25 activity and stability in S. pombe may shed further light on how these pathways interact [4,6,21,29]. Although the coregulation of Cdc25 and Wee1 is crucial for the proper timing of mitosis or cell cycle arrest and is effected via the same pathways [30]; this review will focus mainly on Cdc25 regulation for simplicity.…”

Section: Introductionmentioning

confidence: 99%

Caffeine as a tool for investigating the integration of Cdc25 phosphorylation, activity and ubiquitin-dependent degradation in Schizosaccharomyces pombe

Alao

Sunnerhagen

2020

Cell Div

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The evolutionarily conserved Cdc25 phosphatase is an essential protein that removes inhibitory phosphorylation moieties on the mitotic regulator Cdc2. Together with the Wee1 kinase, a negative regulator of Cdc2 activity, Cdc25 is thus a central regulator of cell cycle progression in Schizosaccharomyces pombe. The expression and activity of Cdc25 is dependent on the activity of the Target of Rapamycin Complex 1 (TORC1). TORC1 inhibition leads to the activation of Cdc25 and repression of Wee1, leading to advanced entry into mitosis. Withdrawal of nitrogen leads to rapid Cdc25 degradation via the ubiquitin- dependent degradation pathway by the Pub1 E3- ligase. Caffeine is believed to mediate the override of DNA damage checkpoint signalling, by inhibiting the activity of the ataxia telangiectasia mutated (ATM)/Rad3 homologues. This model remains controversial, as TORC1 appears to be the preferred target of caffeine in vivo. Recent studies suggest that caffeine induces DNA damage checkpoint override by inducing the nuclear accumulation of Cdc25 in S. pombe. Caffeine may thus modulate Cdc25 activity and stability via inhibition of TORC1. A clearer understanding of the mechanisms by which caffeine stabilises Cdc25, may provide novel insights into how TORC1 and DNA damage signalling is integrated.

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