NEIL3-mediated proteasomal degradation facilitates the repair of cisplatin-induced DNA damage in human cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2023

NEIL3-mediated proteasomal degradation facilitates the repair of cisplatin-induced DNA damage in human cells

Résumé

Anti-neoplastic effect of DNA cross-linking agents such as cisplatin, mitomycin C, and psoralen is attributed to their ability to induce DNA interstrand cross-links (ICLs), which block replication, transcription, and linear repair pathways by preventing DNA strand separation and trigger apoptosis. It is generally agreed that the Fanconi anemia (FA) pathway orchestrates the removal of ICLs by the combined actions of various DNA repair pathways. Recently, attention has been focused on the ability of the NEIL3-initiated base excision repair pathway to resolve psoralen- and abasic site-induced ICLs in an FA-independent manner. Intriguingly, overexpression of NEIL3 is associated with chemo-resistance and poor prognosis in many solid tumors. Here, using loss- and gain-of-function approaches, we demonstrate that NEIL3 confers resistance to cisplatin and participates in the removal of cisplatin–DNA adducts. Proteomic studies reveal that the NEIL3 protein interacts with the 26S proteasome in a cisplatin-dependent manner. NEIL3 mediates proteasomal degradation of WRNIP1, a protein involved in the early step of ICL repair. We propose that NEIL3 participates in the repair of ICL-stalled replication fork by recruitment of the proteasome to ensure a timely transition from lesion recognition to repair via the degradation of early-step vanguard proteins.
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hal-04289483 , version 1 (16-11-2023)

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Umit Aliyaskarova, Yeldar Baiken, Flore Renaud, Sophie Couve, Alexei Kisselev, et al.. NEIL3-mediated proteasomal degradation facilitates the repair of cisplatin-induced DNA damage in human cells. Scientific Reports, 2023, 13 (1), pp.5174. ⟨10.1038/s41598-023-32186-3⟩. ⟨hal-04289483⟩
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