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Journal of Zhejiang University SCIENCE B 2007 Vol.8 No.6 P.377~397


DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis

Author(s):  SCHMITT Estelle, PAQUET Claudie, BEAUCHEMIN Myriam, BERTRAND Richard

Affiliation(s):  Notre Dame Hospital and Montreal Cancer Institute, Research Centre of University of Montreal Hospital Centre (CRCHUM), Montreal (Que) H2L 4M1, Canada; more

Corresponding email(s):   richard.bertrand@umontreal.ca

Key Words:  DNA-damage response network, Cell cycle, Cellular senescence, Apoptosis, Bcl-2 family

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SCHMITT Estelle, PAQUET Claudie, BEAUCHEMIN Myriam, BERTRAND Richard. DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis[J]. Journal of Zhejiang University Science B, 2007, 8(6): 377~397.

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author="SCHMITT Estelle, PAQUET Claudie, BEAUCHEMIN Myriam, BERTRAND Richard",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis
%A SCHMITT Estelle
%A PAQUET Claudie
%J Journal of Zhejiang University SCIENCE B
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%N 6
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%@ 1673-1581
%D 2007
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2007.B0377

T1 - DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis
A1 - SCHMITT Estelle
A1 - PAQUET Claudie
A1 - BERTRAND Richard
J0 - Journal of Zhejiang University Science B
VL - 8
IS - 6
SP - 377
EP - 397
%@ 1673-1581
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.2007.B0377

Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senescence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving “sensor” proteins that sense the damage, and transmit signals to “transducer” proteins, which, in turn, convey the signals to numerous “effector” proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The bcl-2 family of proteins stands among the most crucial regulators of apoptosis and performs vital functions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some bcl-2 family members on cell-cycle checkpoint regulation.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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