c-Myc is necessary for DNA damage-induced apoptosis in the G(2) phase of the cell cycle.

Abstract:

: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 G(2) 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 G(2) 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 G(1) 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.

journal_name

Mol Cell Biol

authors

Adachi S,Obaya AJ,Han Z,Ramos-Desimone N,Wyche JH,Sedivy JM

doi

10.1128/MCB.21.15.4929-4937.2001

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

4929-37

issue

15

eissn

0270-7306

issn

1098-5549

journal_volume

21

pub_type

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