REV7-p53 interaction inhibits ATM-mediated DNA damage signaling

• Published in: Cell cycle (Georgetown, Tex.) Vol. 23; no. 4; pp. 339 - 352
• Main Authors: Biller, Megan, Kabir, Sara, Boado, Chkylle, Nipper, Sarah, Saffa, Alexandra, Tal, Ariella, Allen, Sydney, Sasanuma, Hiroyuki, Dréau, Didier, Vaziri, Cyrus, Tomida, Junya
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 16.02.2024
• Subjects: Ataxia Telangiectasia Mutated Proteins - metabolism; ATM; Cell Line, Tumor; DNA Breaks, Double-Stranded; DNA Damage; DNA double-strand breaks; DNA Repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fanconi anemia; Humans; MAD2B; Phosphorylation; Protein Binding; Signal Transduction; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; ATM; MAD2B; Fanconi anemia; DNA double-strand breaks; DNA repair; p53
• ISSN: 1538-4101; 1551-4005; 1551-4005
• DOI: 10.1080/15384101.2024.2333227

REV7 is an abundant, multifunctional protein that is a known factor in cell cycle regulation and in several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, and DNA Double-Strand Break (DSB) repair pathway choice. Thus far, no direct role has been studied for REV7 in the DNA damage response (DDR) signaling pathway. Here we describe a novel function for REV7 in DSB-induced p53 signaling. We show that REV7 binds directly to p53 to block ATM-dependent p53 Ser15 phosphorylation. We also report that REV7 is involved in the destabilization of p53. These findings affirm REV7's participation in fundamental cell cycle and DNA repair pathways. Furthermore, they highlight REV7 as a critical factor for the integration of multiple processes that determine viability and genome stability.