title: Release from quiescence stimulates the expression of human NEIL3 under the control of the Ras dependent ERK-MAP kinase pathway.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Oslo, Oslo University Hospital, Rikshospitalet, Norway.
authors.forename: Christine Gran
authors.initials: CG
authors.lastname: Neurauter
authors.forename: Luisa
authors.initials: L
authors.lastname: Luna
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D009699:N-Glycosyl Hydrolases / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D016160:Retinoblastoma Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C473634:NEIL1 protein, human; C468764:NEIL3 protein, human; D018631:ras Proteins