A decrease in cyclin B1 levels leads to polyploidization in DNA damage‐induced senescence

Abstract

Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumours. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells frequently show polyploidy. Although abrogation of cell division is thought to correlate with polyploidization, the mechanisms underlying induction of polyploidization in senescent cells are largely unclear. We wished, therefore, to explore the role of cyclin B1 level in polyploidization of Adriamycin-induced senescent cells. A subcytotoxic concentration of Adriamycin induced polyploid cells having the features of senescence, such as flattened and enlarged cell shape and activated beta-galactosidase activity. In DNA damage-induced senescent cells, the levels of cyclin B1 were transiently increased and subsequently decreased. The decrease in cyclin B1 levels occurred in G2 cells during polyploidization upon treatment with a subcytotoxic concentration of Adriamycin. In contrast, neither polyploidy nor a decrease in cyclin B1 levels was induced by treatment with a cytotoxic concentration of Adriamycin. These results suggest that a decrease in cyclin B1 levels is induced by DNA damage, resulting in polyploidization in DNA damage-induced senescence.

Src Family Kinases Promote Silencing of ATR-Chk1 Signaling in Termination of DNA Damage Checkpoint

“…1I), which is reminiscent of results showing that cyclin B1 accumulates during DNA damage-induced G 2 checkpoint arrest and is degraded in mitosis (see Fig. 3A) (61). By contrast, cyclin B1 was found to be degraded during SU6656-induced mitotic slippage.…”

“…Flow Cytometry-Flow cytometric analyses were performed as described previously (56,61). For analysis of Chk1-Ser 317 phosphorylation, HeLa S3 cells were transfected 24 h after seeding.…”

Nuclear translocation of Cyclin B1 marks the restriction point for terminal cell cycle exit in G2 phase

“…19,20 We monitored Cyclin B1-eYFP levels using time-lapse microscopy ( Fig. 1B) and quantified the total fluorescence of multiple positions after careful subtraction of background fluorescence (materials and methods), allowing a time-resolved readout of Cyclin B1-eYFP levels in a population.…”

Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

“…These seemed to be crucial for the execution of mitotic catastrophe [12]. It has been suggested that polyploidization associated with the senescent cell morphology appearing after DNA damage may result from degradation of cyclin B1 [13]. Cell cycle arrest may also be accompanied by alterations in cyclin B1 level.…”