Formaldehyde inhibits UV-induced phosphorylation of histone H2AX

Formaldehyde (FA) is widely known to cause DNA damage. Recently, our study showed that FA can also inhibit a repair process of DNA damage, nucleotide excision repair (NER). DNA damage response (DDR) involving activation of phosphorylation pathways is important for the accuracy of the repair process, and the inhibition of the accurate repair would raise mutation rate, leading to cancer. We herein investigated whether FA influences phosphorylation of histone H2AX (gamma-H2AX), an intermediate player of DDR signaling pathways. Human keratinocytes HaCaT were treated with FA and then exposed to UV known to generate clear gamma-H2AX signal. UV-induced gamma-H2AX was inhibited by FA in a dose-dependent manner. The repair of pyrimidine dimers was inhibited by FA, while the recruitments of gamma-H2AX-related proteins, Mre11 and 53BP1, to damaged sites were also delayed. Mre11, Nbs-1, H2AX and ATM were not degraded after treatment with FA as opposed to NER-related protein, TFIIH. On the other hand, FA inhibited phosphorylation of ATM which acts upstream of gamma-H2AX. These results suggest that FA can affect the repair of DNA damage via inhibition of the phosphorylation pathways of H2AX.