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. Author manuscript; available in PMC: 2016 Jan 1.
Published in final edited form as: Mutat Res Rev Mutat Res. 2014 Oct 22;763:168–180. doi: 10.1016/j.mrrev.2014.10.003

Figure 4. Reversible checkpoint activation requires TLS.

Figure 4

A) Isolated model for checkpoint activation: DNA lesions accumulate randomly in the DNA. A fork that encounters a lesion triggers ATR and Chk1 activation (1). Active Chk1 dissociates from chromatin, inhibiting origin firing and creating a time window for DNA repair (2). DNA repair removes DNA lesions (4’). Chk1 signal is attenuated in the nucleoplasm by multiple mechanisms, including degradation of active Chk1. As a consequence, DNA replication is resumed at inhibited origins (4’) but not at forks in check (5’).

B) A checkpoint and TLS coordination model: when Chk1 is released to control origin firing, it promotes the loading and activation of Pol η at the fork in check (3). As in A), origins are no longer inhibited after active Chk1 is degraded. In contrast to A), Chk1 activation and its release from chromatin enable a TLS-dependent restoration of DNA elongation at forks in check (4). DNA replication is thus resumed after efficient lesion removal, thereby avoiding the collapse of stalled forks (5).