FIGURE 8.

Proposed consequences of Pu-27-induced DNA damage. Pu-27 causes extensive DNA damage telomeric and nontelomeric region directly or indirectly through decreasing expression of c-Myc. This induces γH₂AX, activating DNA damage response regulators leading to G₁ arrest (43), decreased DNA damage repair, and G₂M phase regulatory proteins. Pu-27-induced G₁ arrest provides some time to repair. The cell passes through the cell cycle without repair. Then damaged DNA moves quickly through G₂ arrest without dividing properly at the M phase (as survivin guards the G₂M phase of cell cycle to prevent unwanted apoptosis), leading to cell death perhaps through mitotic catastrophe. Asterisk with thin arrow, cell moves slowly; asterisk with thick arrow, cell moves fast.