FANCJ and RTEL1 facilitate pre-replication complex disassembly following replisome collision
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George Cameron Simran Negi Koichi Sato Sevim Yardimci Cagla Kaya Cameron McClymont Anoop Kumar Yadav Jana Krejci Puck Knipscheer Hana Polasek-Sedlackova Hasan YardimciAbstract
At the onset of eukaryotic DNA replication, double hexamers of MCM2-7 are assembled into inactive pre-replication complexes (pre-RCs) at replication origins. An excess of pre-RCs is loaded onto DNA, but only a fraction becomes activated to form CMG helicases when origins fire. The replisome, built around CMG, must navigate past dormant origins harboring inactive pre-RCs, but the mechanism by which this is achieved is unclear. Here, we used single-molecule imaging to visualize collisions between replisomes and pre-RCs during DNA replication in Xenopus laevis egg extracts. We show that pre-RCs are frequently removed from DNA upon collision and that efficient pre-RC removal requires the accessory helicases FANCJ and RTEL1. Furthermore, simultaneous depletion of both FANCJ and RTEL1 in human cells leads to pre-RC accumulation on chromatin and DNA damage. Together, our findings reveal a role for FANCJ and RTEL1 in pre-RC removal, ensuring efficient replication fork progression and maintaining genome stability.
Journal details
Journal
Cell Reports
Volume
45
Issue number
8
Pages
117860
Available online
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Publisher website (DOI)
10.1016/j.celrep.2026.117860
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Europe PubMed Central
42604558
Pubmed
42604558
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