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- W4366124627 endingPage "102701" @default.
- W4366124627 startingPage "102701" @default.
- W4366124627 abstract "We and others have reported that senescence onset is accompanied by genomic instability that is evident by several defects, such as aneuploidy or erroneous mitosis features. Here, we report that these defects also appear in young cells upon oxidative insult. We provide evidence that these errors could be the consequence of oxidative stress (OS)- either exogenous or senescence-associated - overriding the spindle assembly checkpoint (SAC). Young cells treated with Η2Ο2 as well as older cells fail to maintain mitotic arrest in the presence of spindle poisons and a significant higher percentage of them have supernumerary centrosomes and centrosome related anomalous characteristics. We also report that aging is escorted by expression modifications of SAC components, and especially of Bub1b/BubR1. Bub1b/BubR1 has been previously reported to decrease naturally upon aging. Here, we show that there is an initial increase in Bub1b/BubR1 levels, feasibly as part of the cells' response against OS-driven genomic instability, that is followed by its autophagy dependent degradation. This provides an explanation that was missing regarding the molecular entity responsible for the downregulation of Bub1b/BubR1 upon aging, especially since it is well established, by us and others, that the proteasome function decays as cells age. These results, not only serve the previously reported notion of a shift from proteasome to autophagy-dependent degradation upon aging, but also provide a mechanistic insight for mitotic errors-driven senescence. We believe that our conclusions deepen our understanding regarding the homeostatic function of autophagy that serves the establishment of senescence as a barrier against cellular transformation." @default.
- W4366124627 created "2023-04-19" @default.
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- W4366124627 date "2023-06-01" @default.
- W4366124627 modified "2023-10-17" @default.
- W4366124627 title "The establishment of mitotic errors-driven senescence depends on autophagy" @default.
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- W4366124627 doi "https://doi.org/10.1016/j.redox.2023.102701" @default.
- W4366124627 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37094517" @default.
- W4366124627 hasPublicationYear "2023" @default.
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