Formaldehyde inhibits UV-induced phosphorylation of histone H2AX. (December 2019)

• Record Type: Journal Article
• Authors: Yang, Guang; Komaki, Yukako; Yoshida, Ikuma; Ibuki, Yuko
• Is Part Of: Toxicology in vitro. Volume 61(2019)
• Publication Date: 2019-12
• Subjects: Formaldehyde -- Ultraviolet rays -- γ-H2AX -- Nucleotide excision repair -- 6–4 photoproducts -- ATM; ATM ataxia telangiectasia mutated -- ATR ataxia telangiectasia and Rad3-related -- DDR DNA damage response -- ssDNA single stranded DNA -- BER base excision repair -- BSFGE biased sinusoidal field gel electrophoresis -- CBB Coomassie Brilliant Blue -- DMEM Dulbecco's modified Eagle's medium -- DSBs double strand breaks -- FA formaldehyde -- FBS fetal bovine serum -- IARC International Agency for Research on Cancer -- NER nucleotide excision repair -- 6-4PPs 6–4 photoproducts -- CPDs cyclobutane pyrimidine dimers -- PI propidium iodide -- SEM semicarbazide; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2019.104687
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: 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 (γ-H2AX), an intermediate player of DDR signaling pathways. Human keratinocytes HaCaT were treated with FA and then exposed to UV known to generate clear γ-H2AX signal. UV-induced γ-H2AX was inhibited by FA in a dose-dependent manner. The repair of pyrimidine dimers was inhibited by FA, while the recruitments of γ-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 γ-H2AX. These results suggest that FA can affect the repair of DNA damage via inhibition of the phosphorylation pathways of H2AX. Graphical abstract: Unlabelled Image Highlights: FA inhibited UV-induced γ-H2AX. The repair of UV-generated DNA damage was inhibited by FA. The recruitments of γ-H2AX-related proteins to damaged sites were delayed. FA inhibited phosphorylation of ATM which acts upstream of γ-H2AX. The multiple inhibition pathways of γ-H2AX may contribute to the FA carcinogenecity.