O6-Methylguanine-DNA methyltransferase (MGMT) gene expression is associated with ultraviolet B (UVB)-induced cell growth inhibition and recovery

Abstract

UV irradiation causes cellular damage, with DNA being especially susceptible. A variety of cellular responses including damage repair, cell cycle arrest, senescence, and apoptosis can occur immediately after exposure to UV irradiation. During subsequent repair processes, cell growth is suppressed to facilitate repair. O6-Methylguanine-DNA methyltransferase (MGMT) is a repair molecule that removes methyl groups from chemotherapeutic agent-induced methylated nucleotide. Recently, it has been reported that inhibition of MGMT suppresses proliferation of cancer cells and UV irradiation regulates expression of MGMT. In the current study, we investigated a potential role of MGMT during UVB-induced cell damage and repair. MGMT expression was transiently down-regulated during UVB-induced suppression of cell growth, but returned to normal levels coinciding with recovery of UVB-induced inhibition of cell growth. In addition, the recovery of UVB-induced proliferative suppression was delayed in response to treatment with the MGMT inhibitor O6-benzylguanine. Both ATM and p53 were activated during UVB-induced transient down-regulation of MGMT, suggesting that the regulation of MGMT expression is mediated via ATM and p53-dependent signal transduction. Based on these results, we propose that regulation of MGMT expression is associated with UVB-induced cell growth suppression and recovery. ？ 2015, The Genetics Society of Korea and Springer-Science and Media.