Unresolved stalled ribosome complexes restrict cell-cycle progression after genotoxic stress
0301 basic medicine
ribosome stalling
0303 health sciences
ribosome-associated quality control
RNA-binding protein
cell-cycle arrest
ultraviolet light
RNA damage
Article
3. Good health
03 medical and health sciences
Protein Biosynthesis
Humans
ASC-1 complex
RNA, Messenger
Ribosomes
DNA Damage
DOI:
10.1016/j.molcel.2022.01.019
Publication Date:
2022-02-17T15:34:08Z
AUTHORS (9)
ABSTRACT
During the translation surveillance mechanism known as ribosome-associated quality control, ASC-1 complex (ASCC) disassembles ribosomes stalled on mRNA. Here, we show that there are two distinct classes of ribosome. Ribosomes by elongation inhibitors or methylated mRNA short lived in human cells because they split ASCC. In contrast, although ultraviolet light and 4-nitroquinoline 1-oxide induce ribosome stalling damaging mRNA, ASCC is recruited to these ribosomes, found refractory Consequently, unresolved UV- 4NQO-stalled persist cells. We activates cell-cycle arrest, partly through ZAK-p38MAPK signaling, this delay prolonged when cannot resolve ribosomes. Thus, propose sensitivity influences kinetics stall resolution, which turn controls adaptive stress response.
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