RAD51 m6A and PARylation modification orchestrate benzene-induced haematological toxicity

It is well-established that occupational benzene exposure can cause leukemia. DNA damage repair has great potential in assessing the health risk of benzene, but the role of RAD51, an executor of DNA damage repair, remains unclear in benzene-induced hematotoxicity. Here, we demonstrate that exposure to hydroquinone (HQ), a key metabolite of benzene, upregulates RAD51 expression in human lymphoblast (TK6), consequently suppressing DNA damage. Mechanistically, we demonstrate that METTL3, an m6A methyltransferase, catalyzes m6A modification on RAD51 mRNA, and that the m6A reader protein YTHDC1 subsequently enhances its expression. Moreover, PARP1-mediated PARylation at the glutamic acid 59 residue of RAD51 further suppresses HQ-induced DNA damage. We also observed the upregulated expression of PARP1, YTHDC1, METTL3, and RAD51 in peripheral blood lymphocytes from occupationally benzene-exposed workers. Collectively, these findings suggest that RAD51 may represent a promising biomarker for monitoring benzene-induced haematological toxicity in environmentally exposed populations.