Participation of ATM, SMG1, and DDX5 in a DNA Damage-Induced Alternative Splicing Pathway

• DOI: 10.1667/rade-22-00219.1
• Publication Date: 2023-03-15T21:02:43Z
• Authors: Jennifer J. McCann; Donald E. Fleenor; Jing Chen; Chun-Hsiang Lai; Thomas E. Bass; Michael B. Kastan
• Keywords: Splicing factor; RNA Helicase A

Altered cellular responses to DNA damage can contribute cancer development, progression, and therapeutic resistance. Mutations in key response factors occur across many types, the damage-responsive gene, TP53, is frequently mutated a high percentage of cancers. We recently reported that an alternative splicing pathway induced by regulates TP53 RNA further modulates stress responses. Through damage-induced inhibition SMG1 kinase, pre-mRNA alternatively spliced generate TP53b mRNA p53b protein required for optimal induction senescence after ionizing radiation-induced damage. Herein, we confirmed extended these observations demonstrating ATM kinase repression activity radiation. found helicase factor, DDX5, interacts with SMG1, TP53c mRNAs damage, contributes senescence. Interestingly, role p53 appears be distinguishable from its regulating nonsense-mediated decay. Thus, ATM, DDX5 participate