Overview of Biological Responses to DNA Damage

Temporally, we divide the biological responses to DNA damage into three stages the immediate early responses, which most likely occur without the requirement for new gene expression the early responses and the late responses, which are mostly irreversible (Fig. IB). 

The late responses to DNA damage are irreversible. These irreversible outcomes include clonogenic survival, adaptation, and death (mitotic death, apoptotic death, mitotic catastrophe). 

Master Switch PIKK Family of Protein Kinases 

Members of the PIKK family are not the only protein kinases involved in DNA damage response. Two other protein kinases, Ghkl and Ghk2, are also conserved through evolution and play important roles in regelating DNA damage responses (Bartek and Lukas, 2003). 

The knockout of Chkl causes early embryonic lethality (Liu et al, 2000a), indicating that the mammalian Ghkl kinase is required for viability. This essential function of Ghkl may reflect a continual dependence of 

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