It is generally accepted that DNA damage checkpoint is the mechanism that allows time for DNA damage repair. However, several lines of evidence challenge this paradigm, especially, in the case of G1 checkpoint. The first evidence is the compete difference between the repair kinetics of DNA double-strand breaks (very rapid) and the timing of G1 checkpoint induction (very slow) after ionizing radiation. The second evidence is that inactivation of p53, which is a central payer of G1 checkpoint, does not render cells radiosensitive, rather, such cells become radioresistant. Moreover, it was shown that G1 arrest persists almost permanently after irradiation, until the time when most of the initial damage should be repaired and disappear. Therefore, cells should have a mechanism to maintain G1 checkpoint signaling by amplifying the signal from a limited number of damage. In this review, we discuss what is the bona fide role of G1 arrest and how G1 checkpoint signal is maintained long after irradiation.
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