Data Sheet 1_Loss of lactate dehydrogenase A disrupts R-loop homeostasis and induces DNA damage in breast cancer cells.zip

Exogenous lactate failed to rescue these R-loop perturbations, suggesting that LDHA regulates R-loops through a mechanism beyond its metabolic activity. Genomic analysis revealed partial overlap between LDHA-binding sites and R-loop-prone regions, indicating a potential direct role of LDHA in R-loop formation. Transcriptomic profiling showed widespread gene expression changes following LDHA loss, although only four genes were associated with both LDHA binding and R-loop peaks.

Importantly, LDHA knockout induced accumulation of R-loop foci and DNA damage, both of which were reversed by RNase H1 expression.</p>Discussion<p>These findings identify LDHA as a novel regulator of R-loops and suggest that it may influence R-loop homeostasis through direct DNA binding rather than solely through its enzymatic role in glycolysis. Further studies are needed to elucidate the molecular mechanism underlying LDHA-mediated R-loop regulation.</p>