Produção Nacional
Revisado por pares
A DNA repair-independent role for alkyladenine DNA glycosylase in alkylation-induced unfolded protein response
2022; National Academy of Sciences; Volume: 119; Issue: 9 Linguagem: Inglês
10.1073/pnas.2111404119
ISSN1091-6490
AutoresLarissa Milano, Clara Forrer Charlier, Rafaela Rafognatto Andreguetti, Thomas C. Cox, Eleanor Healing, Marcos Paulo Machado Thomé, Ruan Elliott, Leona D. Samson, Jean‐Yves Masson, Guido Lenz, João Antônio Pêgas Henriques, Axel Nohturfft, Lisiane B. Meira,
Tópico(s)Autophagy in Disease and Therapy
ResumoAlkylating agents damage DNA and proteins and are widely used in cancer chemotherapy. While cellular responses to alkylation-induced DNA damage have been explored, knowledge of how alkylation affects global cellular stress responses is sparse. Here, we examined the effects of the alkylating agent methylmethane sulfonate (MMS) on gene expression in mouse liver, using mice deficient in alkyladenine DNA glycosylase (Aag), the enzyme that initiates the repair of alkylated DNA bases. MMS induced a robust transcriptional response in wild-type liver that included markers of the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) known to be controlled by XBP1, a key UPR effector. Importantly, this response is significantly reduced in the
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