| Autor: |
Lucca, Chiara, Ferrari, Elisa, Shubassi, Ghadeer, Ajazi, Arta, Choudhary, Ramveer, Bruhn, Christopher, Matafora, Vittoria, Bachi, Angela, Foiani, Marco |
| Zdroj: |
Cell Reports; June 2024, Vol. 43 Issue: 6 |
| Abstrakt: |
Survival from UV-induced DNA lesions relies on nucleotide excision repair (NER) and the Mec1ATRDNA damage response (DDR). We study DDR and NER in aging cells and find that old cells struggle to repair DNA and activate Mec1ATR. We employ pharmacological and genetic approaches to rescue DDR and NER during aging. Conditions activating Snf1AMPKrescue DDR functionality, but not NER, while inhibition of the TORC1-Sch9S6Kaxis restores NER and enhances DDR by tuning PP2A activity, specifically in aging cells. Age-related repair deficiency depends on Snf1AMPK-mediated phosphorylation of Sch9S6Kon Ser160 and Ser163. PP2A activity in old cells is detrimental for DDR and influences NER by modulating Snf1AMPKand Sch9S6K. Hence, the DDR and repair pathways in aging cells are influenced by the metabolic tuning of opposing AMPK and TORC1 networks and by PP2A activity. Specific Sch9S6Kphospho-isoforms control DDR and NER efficiency, specifically during aging. |
| Databáze: |
Supplemental Index |
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