Loss of lactate dehydrogenase A disrupts R-loop homeostasis and induces DNA damage in breast cancer cells.

Loss of LDHA in breast cancer cells disrupts R-loop homeostasis, causing increased R-loop accumulation and DNA damage, with 199 peaks rising and 81 decreasing.

• Why it matters: Understanding R-loop regulation is crucial because their imbalance can lead to genome instability and cancer progression; the role of LDHA in this process was previously unclear.
• What they did: Researchers used CUT&Tag-seq, RNA-seq, immunofluorescence, and Western blotting to compare wild-type and LDHA knockout 4T1 cells, revealing LDHA’s direct involvement in R-loop regulation.
• The result: LDHA loss caused R-loop accumulation and DNA damage, which could be reversed by RNase H1, indicating LDHA’s role in maintaining genomic stability beyond its metabolic function.