Phosphoproteomics of ATR signaling in mouse testes

• DOI: 10.7554/elife.68648
• Publication Date: 2022-02-08T15:00:20Z
• Authors: Jennie R Sims; Vitor M Faça; Catalina Pereira; Carolline Ascenção; William Comstock; Jumana Badar; Gerardo A Arroyo-...; Raimundo Freire; Paula E Cohen; Robert S Weiss; Marcus B Smolka
• Keywords: Phosphoproteomics

The phosphatidylinositol 3′ kinase (PI3K)‐related ATR is crucial for mammalian meiosis. promotes meiotic progression by coordinating key events in DNA repair, sex chromosome inactivation (MSCI), and checkpoint-dependent quality control during prophase I. Despite its central roles meiosis, the ATR-dependent signaling network remains largely unknown. Here, we used phosphoproteomics to define testes from mice following chemical genetic ablation of signaling. Quantitative analysis phosphoproteomes obtained after germ cell-specific activating 9-1-1 complex or treatment with inhibitor identified over 14,000 phosphorylation sites samples, which 401 were found be dependent on both ATR. Our analyses damage repair proteins including TOPBP1, SMC3, MDC1, RAD50, SLX4. Importantly, RAD1-dependent involved mRNA regulatory processes, SETX RANBP3, whose localization body was lost upon inhibition. In addition identifying expected ATR-targeted S/T-Q motif, enrichment an S/T-P-X-K motif set events, suggesting that via proline-directed kinase(s) Indeed, important proper CDK2 spermatocytes. Overall, our establishes a map mouse highlights potential meiotic-specific actions I progression.