Biology subjects

Reisz, J. R.

Publications and source records attributed to Reisz, J. R..

2 recordsLinked to original sources

bioRxiv2026

Choline kinase A is required for alkylating agent resistance via lipid droplet formation

Tolerance of DNA damage promotes cellular fitness, particularly in cancer cells under chemotherapeutic pressure. However, the biology and regulation of DNA damage responses remain incompletely understood. Using an unbiased genetic screen, we found that choline kinase A (CHKA) is required for alkylating resistance in T-cell acute lymphoblastic leukemia (T-ALL). CHKA is best-known as a cytoplasmic enzyme that catalyzes the first step in phosphatidylcholine biosynthesis, but alkylating agent resistance was mediated by a nuclear function of CHKA. We found that CHKA positively regulates transcription of the DNA repair factor RAD51 via formation of lipid droplets. Restoring lipid droplet formation or RAD51 expression was sufficient to confer alkylating agent resistance despite CHKA inactivation. Our findings link lipid droplet formation to transcriptional control of the DNA damage response, providing a mechanism through which cellular lipid metabolism can control the maintenance of genome integrity.

cell biology↗

bioRxiv2025

Integrative Multi-Omics Analysis Identifies Nuclear Factor I as a Key Driver of Dysregulated Purine Metabolism in DIPG

Diffuse intrinsic pontine glioma (DIPG) is a devastating brainstem cancer in children, with a median survival of under one year and limited treatment options. Over 80% of DIPGs possess a H3K27M mutation. To identify metabolic vulnerabilities linked to this mutation, we utilized a multi-omics approach in H3K27M-expressing cells, patient-derived cell lines, and mouse models. We show that by reprogramming chromatin landscape the mutation aberrantly induces NFI transcriptional activity, leading to misregulated purine metabolism. The mutation amplifies purine biosynthesis and degradation via the enzymes ATIC and PNP, respectively. Unregulated purine degradation relieves the negative feedback of purines on their own synthesis allowing continuous synthesis, use and degradation making DIPGs reliant on purine biosynthesis. Targeting ATIC reduced tumor progression and improved survival in mice. We propose ATIC as a potential novel target in DIPG.

cancer biology↗