Duolink image tool6/24/2023 Stabilizes replication forks for genome integrity ( 3– 5).Īnother is a damage tolerance mechanism termed translesion DNA It then causes the phosphorylation andĪctivation of downstream checkpoint kinase 1 (Chk1), which in turn Recruited on ssDNA where it is coated with ssDNA-binding protein, The checkpoint kinase ATM and Rad3-related (ATR) is SsDNA at stalled replication forks, attributed to a deficiency inĭNA synthesis. The S-phase checkpoint response, which is evoked by an exposed To preserve genome integrity during chromosome replication,Įukaryotic cells have acquired several adaptive responses to DNAĭamage ( 1, 2). Major cause of deleterious lesions, such as DNA double-strandīreaks. In excessive formation of single-strand DNA (ssDNA) that could be a Interfere with the progress of replication forks and thereby result Maintaining genome integrity, as unrepaired DNA lesions at S phase These findings provide novel insights into the molecular mechanism underlying the participation of CTF18‑RFC in the regulation of replication stress response.Ĭhromosome replication is a risky process for Furthermore, the PLA demonstrated that the kinetics of the interaction between CTF18 and RPA was positively correlated with that of checkpoint kinase 1 phosphorylation, which is an indicator of activation of the ATM and Rad3‑related pathway. Similar results were obtained after exposure to ultraviolet irradiation, which triggers translesion DNA synthesis. Using an in situ proximity ligation assay (PLA), it was demonstrated that the interaction between CTF18 and RPA occurs in chromatin when replication stress is elicited by treatment with hydroxyurea during S phase. The present study demonstrated that endogenous CTF18 forms a physical complex with a single‑stranded DNA‑binding protein replication protein A (RPA) in mammalian cells. However, it remains largely unknown how CTF18‑RFC responds to replication stress and is recruited to stalled replication forks. An alternative clamp loader complex termed chromosome transmission fidelity protein 18 and replication factor C (CTF18‑RFC) has been shown to act as a positive regulator of two types of replication stress response: S‑phase checkpoint signaling and translesion DNA synthesis. Replication stress response is a protective mechanism against defects in chromosome replication for maintaining genome integrity in eukaryotic cells.
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