Modeling the 3D Spatiotemporal Organization of Chromatin Replication

G. Forte, S. Buonomo, P. R. Cook, N. Gilbert, D. Marenduzzo, Enzo Orlandini

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

We propose a polymer model to investigate in silico the dynamics of chromatin replication in three dimensions (PolyRep). Our results indicate that replication complexes, the replisomes, may self-assemble during the process and replicate chromatin by extruding it (immobile replisome) or by moving along the template filament (tracking replisome), reconciling previous discordant experimental evidence in favour of either scenario. Importantly, the emergence of one of the two morphologies depends in a major way on the replication origin distribution as well as on the presence of nonspecific interactions between unreplicated chromatin and firing factors—polymerases and other components of the replisome. Nonspecific interactions also appear instrumental to creating clusters of factors and replication forks, structures akin to the replication foci observed in mammalian cells in vivo. PolyRep simulations predict different mechanisms for foci evolution, including unanticipated loop-mediated fusion dynamics. We suggest that cluster formation, which our model suggests to be a generic feature of chromatin replication, provides a hitherto underappreciated but robust pathway to avoid stalled or faulty forks, which would otherwise diminish the efficiency of the replication process.
Original languageEnglish
Article number033014
Number of pages11
JournalPRX Life
Volume2
Issue number3
DOIs
Publication statusPublished - 26 Sept 2024

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