title: Protective roles of Gadd45 and MDM2 in blueberry anthocyanins mediated DNA repair of fragmented and non-fragmented DNA damage in UV-irradiated HepG2 cells.
abstract: Growth Arrest and DNA Damage-inducible 45 (Gadd45) and MDM2 proteins, together with p21 and p53, play important roles in cell cycle checkpoints, DNA repair, and genome integrity maintenance. Gadd45 and MDM2 were activated and transcribed instantly by UV irradiation, whereas blueberry anthocyanins (BA) decreased the gene and protein expression levels in HepG2 cells for up to 24 h, and gradually restored the UV-induced fragmented and non-fragmented DNA damage of the nucleus at a time point of 12 h. Nevertheless, UV-irradiated HepG2 cell arrests occurred mainly in the G1 phase, which indicated G1 as a checkpoint. The proteins, p21 and p53, retain cellular integrity, suppressing the oncogenic transformation by interruption of the G1 phase of the cellular cycle, giving time for repairing the damage to DNA, or apoptosis induction if the damage is too severe to be repaired, while MDM2 and Gadd45 concomitantly ensure the presence of p53 and p21. Thus, we conclude that repair, together with Gadd45 and MDM2 genes, were involved in light and dark reaction mechanisms, however, BA could interfere and assist the repair through restoration, although further studies of the complex of the gene cascades triggered and responded to in BA-assisted DNA repair are needed.
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China. Luo58@yahoo.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Lu
authors.forename: Guangyang
authors.initials: G
authors.lastname: He
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Maonian
authors.initials: M
authors.lastname: Xu
authors.forename: Jingkai
authors.initials: J
authors.lastname: Zhang
authors.forename: Meiling
authors.initials: M
authors.lastname: Li
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.forename: Zhenjing
authors.initials: Z
authors.lastname: Li
authors.forename: Likui
authors.initials: L
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
mesh_terms: D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D029798:Blueberry Plants / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D056945:Hep G2 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000872:Anthocyanins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53; D020741:rho GTP-Binding Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C495901:TP53 protein, human; C497206:MDM2 protein, human