Logic of a mammalian metabolic cycle: an oscillated NAD+/NADH redox signaling regulates coordinated histone expression and S-phase progression.
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.
Yu
Fa-Xing
FX
Institute of Molecular and Cell Biology, Singapore, Singapore.
Dai
Ru-Ping
RP
Goh
Shuang-Ru
SR
Zheng
Lei
L
Luo
Yan
Y
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
D019927:Cyclin E; D006657:Histones; D009243:NAD; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2