Protective role of histone deacetylase 4 from ultraviolet radiation‐induced DNA lesions

Abstract

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.

Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes

“…Besides HDAC1 and HDAC2 [122], additional histone deacetylation steps by HDAC3 and HDAC4 have been implicated in GG-NER. In fact, all four HDACs were found to stimulate recruitment of XPC to UV-induced DNA lesions [125][126][127], possibly by lowering the inhibitory impact of histone acetylation on XPC binding to nucleosomes [125] (Fig. 4).…”

“…There are no detectable interactions between HDAC3 and XPC [127] HDAC4 HDAC4 interacts with XPC. The recruitment of XPC to photolesions is stimulated by HDAC4-mediated deacetylation [126] INO80 XPC recruitment is stimulated by the DDB1-mediated interaction with the chromatin remodeler INO80…”

“…There are no detectable interactions between HDAC3 and XPC [ 127 ] HDAC4 HDAC4 interacts with XPC. The recruitment of XPC to photolesions is stimulated by HDAC4-mediated deacetylation [ 126 ] INO80 XPC recruitment is stimulated by the DDB1-mediated interaction with the chromatin remodeler INO80 [ 67 ] PARP1 XPC and PARP1 interact. The recruitment of XPC to DNA lesions is stimulated by PARP1-mediated PARylation [ 34 , 71 ] DDB2 The SUMOylation of DDB2 at K309 stimulates XPC recruitment to sites of local UV damage [ 41 ] …”

“…4 ). Although the precise recruitment mechanism of HDAC3 and HDAC4 and the potential involvement of DDB2 are currently unclear, HDAC3 was specifically linked to H3K14 deacetylation in response to UV irradiation, which was found to stimulate CPD repair in chromatin [ 126 , 127 ]. How the HBO1-dependent H3K14 acetylation and the HDAC3-dependent H3K14 deacetylation are orchestrated and synergize to stimulate CPD repair remains to be elucidated.…”

Increased histone H3 acetylation inhibit the inflammatory response and activate the serum immunity of Pearl oyster Pinctada fucata martensii

“…Sirt1 can control the self-renewal and proliferation of mouse embryonic stem cells by regulating the deacetylation of p53 (Han et al, 2005). HDAC4 interacts with the nucleotide excision repair factor XPC, which plays an important role in effectively removing the ultraviolet Binduced DNA damage (Li et al, 2020). HDAC6 plays a crucial role in the innate immune response to intracellular bacterial infection through Toll-like receptor-mediated signaling (Ran and Zhou, 2019).…”