Open Accessc-Myc Is Necessary for DNA Damage-Induced Apoptosis in the G2 Phase of the Cell Cycle
Author(s) -
Susumu Adachi,
Álvaro J. Obaya,
Zhiyong Han,
Noemi RAMOSDeSIMONE,
James H. Wyche,
John M. Sedivy
Publication year - 2001
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.21.15.4929-4937.2001
Subject(s) - biology , cell cycle , ectopic expression , apoptosis , dna damage , microbiology and biotechnology , cyclin , cyclin a , cyclin d1 , transcription factor , dna fragmentation , cyclin e , cyclin b , cancer research , programmed cell death , dna , gene , genetics
The c-myc proto-oncogene encodes a transcription factor that participates in the regulation of cellular proliferation, differentiation, and apoptosis. Ectopic overexpression of c-Myc has been shown to sensitize cells to apoptosis. We report here that cells lacking c-Myc activity due to disruption of the c-myc gene by targeted homologous recombination are defective in DNA damage-initiated apoptosis in the G2 phase of the cell cycle. The downstream effector of c-Myc is cyclin A, whose ectopic expression in c-myc −/− cells rescues the apoptosis defect. The kinetics of the G2 response indicate that the induction of cyclin A and the concomitant activation of Cdk2 represent an early step during commitment to apoptosis. In contrast, expression of cyclins E and D1 does not rescue the apoptosis defect, and apoptotic processes in G1 phase are not affected in c-myc −/− cells. These observations link DNA damage-induced apoptosis with cell cycle progression and implicate c-Myc in the functioning of a subset of these pathways.