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Figure 1 | Cell Division

Figure 1

From: Chk1 suppressed cell death

Figure 1

Chk1 suppressed death pathways. Chk1 responds to DNA replication stress in an ATR-dependent manner to trigger S-phase checkpoints, suppress inappropriate firing of late or cryptic DNA replication origins, and maintain replication fork integrity. When this ATR-Chk1 signalling pathway is suppressed cells show an enhanced level of apoptosis that appears to be the result of loss of control of replication origin firing [37]. This death pathway is characterized by mitochondrial outer membrane permeabilization (MOMP) and caspase-3 activation but is independent of p53 status [30]. The induction of apoptosis in p53 proficient cells is strongly ATM/p53-dependent. This death pathway characterized by the p53-dependent induction of the proapoptotic proteins PUMA and BAX, MOMP, and caspase-3 activation. p53 deficient cells have a much reduced death response following exposure to IR due to the protective effects of ATM- or ATR-mediated signalling pathways. However in the absence of Chk1, such cells show a caspase-2-dependent apoptotic response that that bypasses Bcl-2, MOMP, and caspase-3 [31]. How caspase-2 triggers apoptosis is unclear as previous work suggests caspase-2 induces death through BID cleavage and MOMP [36]. In the p53-/-Chk1 depleted cells this death pathway is not activated (X) by IR.

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