Unresolved stalled ribosome complexes restrict cell-cycle progression after genotoxic stress

• DOI: 10.1016/j.molcel.2022.01.019
• Publication Date: 2022-02-17T15:34:08Z
• Authors: Mark Stoneley; Robert F. Harvey; Thomas E. Mulroney; Ryan Mordue; Rebekah Jukes-Jones; Kelvin Cain; Kathryn S. Lilley; Ritwick Sawarkar; Anne E. Willis
• Keywords: 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

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.