Open AccessGenetic instability in cancer cells by impaired cell cycle checkpoints
Author(s) -
Nakanishi Makoto,
Shimada Midori,
Niida Hiroyuki
Publication year - 2006
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2006.00289.x
Subject(s) - dna damage , mitotic catastrophe , microbiology and biotechnology , biology , genome instability , dna re replication , chromatin , dna repair , cell cycle checkpoint , cell cycle , mitosis , dna replication , dna , cancer research , cancer , genetics , eukaryotic dna replication
Cells continuously encounter DNA damage caused either by damaging agents, including oxygen radicals and DNA replication errors caused by stalled replication forks, or by extracellular environments such as ultraviolet or ionizing irradiation. Such DNA damage poses a great threat to genome stability, potentially leading to loss or amplification of chromosome activity, which may result in cellular senescence, cancer or apoptosis. The DNA damage checkpoints coordinate an arrest in cell cycle progression with the DNA repair process, suppressing either mitotic catastrophe or proliferation of cells with damaged DNA. Numerous key players have been identified in terms of damage sensor proteins, transducer kinases and effectors, but their coordination and interconnectedness in damage control have only recently become evident. In this review, we discuss changes in chromatin structure, recruitment of mediator proteins and activation of transducer kinases in response to DNA damage. These cellular responses are important for determining the potential effects of current cancer therapies in terms of toxicity and efficacy. ( Cancer Sci 2006; 97: 984–989)