DNA damage checkpoint control in cells exposed to ionizing radiation

被引:387
作者
Iliakis, G
Wang, Y
Guan, J
Wang, HC
机构
[1] Univ Essen Med Sch, Inst Med Radiat Biol, D-45122 Essen, Germany
[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA
关键词
checkpoints; DNA repair; DNA double-strand breaks; ionizing radiation;
D O I
10.1038/sj.onc.1206682
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Damage induced in the DNA after exposure of cells to ionizing radiation activates checkpoint pathways that inhibit progression of cells through the G1 and G2 phases and induce a transient delay in the progression through S phase. Checkpoints together with repair and apoptosis are integrated in a circuitry that determines the ultimate response of a cell to DNA damage. Checkpoint activation typically requires sensors and mediators of DNA damage, signal transducers and effectors. Here, we review the current state of knowledge regarding mechanisms of checkpoint activation and proteins involved in the different steps of the process. Emphasis is placed on the role of ATM and ATR, as well on CHK1 and CHK2 kinases in checkpoint response. The roles of downstream effectors, such as P53 and the CDC25 family of proteins, are also described, and connections between repair and checkpoint activation are attempted. The role of checkpoints in genomic stability and the potential of improving the treatment of cancer by DNA damage inducing agents through checkpoint abrogation are also briefly outlined.
引用
收藏
页码:5834 / 5847
页数:14
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