Release from quiescence stimulates the expression of human NEIL3 under the control of the Ras dependent ERK–MAP kinase pathway

• Published in: DNA repair 2012-04, Vol.11 (4), p.401-409
• Main Authors: Neurauter, Christine Gran, Luna, Luisa, Bjørås, Magnar
• Format: Article
• Language: English
• Subjects: Bacteriology; Base excision repair; Biological and medical sciences; Cell Cycle; Cell cycle regulation; Cell cycle, cell proliferation; Cell Line; Cell physiology; DNA glycosylase; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Growth, nutrition, cell differenciation; Humans; MAP kinase; MAP Kinase Signaling System; Microbiology; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; N-Glycosyl Hydrolases - genetics; N-Glycosyl Hydrolases - metabolism; NEIL3; Promoter Regions, Genetic - genetics; ras Proteins - metabolism; Retinoblastoma Protein - metabolism; Transcription, Genetic
• ISSN: 1568-7864; 1568-7856
• DOI: 10.1016/j.dnarep.2012.01.007

► Human NEIL3 mRNA levels, protein and DNA glycosylase activity is induced upon proliferative stimulation. ► Induction of hNEIL3 expression is under the control of the Ras dependent ERK–MAP kinase pathway. ► Human NEIL3 promoter contains characteristic promoter elements of cell cycle-regulated genes. ► mRNA expression pattern is different for hNEIL1, hNEIL2 and hNEIL3. Base excision repair (BER) is believed to be the predominant pathway for the repair of oxidative DNA damage. BER is initiated by lesion-specific DNA glycosylases that recognize and remove the damaged base. NEIL1, NEIL2 and NEIL3 are three mammalian members of the Fpg/Nei DNA glycosylase family with similar enzymatic properties. In this study we showed that both the transcription and protein levels of hNEIL3 fluctuated during the cell cycle. Based on predicted promoter elements of cell cycle-regulated genes and microarray data from various reports, we suggest that hNEIL3 repression in quiescent cells might be mediated by the DREAM (DP1, RB p130, E2F4 and MuvB core complex) complex. Release from G0 by mitogenic stimulation showed an induction of hNEIL3 in early S phase under the control of the Ras dependent ERK–MAP kinase pathway. In contrast, the total expression of hNEIL1 was downregulated upon release from quiescence while the expression of hNEIL2 was cell cycle independent. Notably, hNEIL3 showed a similar regulation pattern as the replication protein hFEN1 supporting a function of hNEIL3 in replication associated repair. Thus, it appears that specialized functions of the NEILs are ensured by their expression patterns.