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. Author manuscript; available in PMC: 2023 Apr 1.
Published in final edited form as: Pharmacol Res. 2022 Mar 5;178:106162. doi: 10.1016/j.phrs.2022.106162

Figure 2. Role of the ATR/CHK1/WEE1 pathway in replication fork protection.

Figure 2.

In response to replication stress, the replication fork stalls at the site of damage. Stalled replication forks are unstable structures that can cause the fork to collapse and generate DNA double-stranded breaks. After fork stalling, single-stranded DNAs are coated by RPA, which activates ATR. ATR further phosphorylates the replication fork remodeler SMARCAL1 and RAD51 for replication fork reversal. The reversed forks are protected by several fork protectors from deleterious nuclease-mediated fork degradation that can destabilize stalled forks. During DNA replication, the ATR/CHK1/WEE1 pathway protects stalled replication forks by phosphorylating RAD51 and other fork protectors (e.g., BRCA2 and FANCD2) as well as inhibiting nucleases (e.g., EXO1, MUS81, and MRE11) that degrade stalled replication forks.