Oxidative stress overrides the spindle checkpoint.
Aneuploidy, an abnormal chromosome set, can ensue from failure of the spindle checkpoint, the safeguard mechanism that halts anaphase onset until mitotic spindle assembly. Inefficiency of cells to maintain the normal chromosome set across cell generations has been linked to tumorigenesis and senescence. Here we show that oxidative stress overrides the spindle checkpoint mechanism. Oxidant challenge of checkpoint-arrested cells led to proteolysis of the anaphase inhibitor securin and mitotic cyclins. This appeared consequent to loss of cyclin B-cdk1 activity caused by oxidant-induced reversal of cdk1 inhibitory phosphorylation. These observations may provide a link between aneuploidy occurrence and oxidative stress.
D'Angiolella
Vincenzo
V
Faculty of Biotechnological Sciences, Dipartimento di Biologia e Patologia Molecolare e Cellulare L. Califano, University of Napoli Federico II, Napoli, Italy.
Santarpia
Concetta
C
Grieco
Domenico
D
D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D056744:Cyclin B1; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D008941:Spindle Apparatus / Q000235:genetics* / Q000378:metabolism*
D056744:Cyclin B1; D016877:Oxidants; D018844:Cyclin-Dependent Kinases