title: Logic of a mammalian metabolic cycle: an oscillated NAD+/NADH redox signaling regulates coordinated histone expression and S-phase progression.
abstract: Many biological activities naturally oscillate. Here, we show that the NAD(+)/NADH ratios (redox status) fluctuate during mammalian cell cycle, with the S-phase redox status being the least oxidative. The S-phase NAD(+)/NADH redox status gates histone expression and S-phase progression, and may provide a genome protection mechanism during S-phase DNA replication as implicated in yeast. Accordingly, perturbing the cellular redox inhibits histone expression and leads to S-phase arrest. We propose that the S-phase NAD(+)/NADH redox status constitutes a redox signaling, which along with the cyclin E/cdk2 signaling regulates histone expression and S-phase progression.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore, Singapore.
authors.forename: Fa-Xing
authors.initials: FX
authors.lastname: Yu
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Dai
authors.forename: Shuang-Ru
authors.initials: SR
authors.lastname: Goh
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D016196:S Phase; D015398:Signal Transduction
chemical_list: D019927:Cyclin E; D006657:Histones; D009243:NAD; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2