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bioRxiv · 10.1101/2023.03.31.535086

RIF1 regulates replication origin activity and early replication timing in B cells

Malzl, D.·Peycheva, M.·Rahjouei, A.·Gnan, S.·Klein, K.·Nazarova, M.·Schoeberl, U. E.·Gilbert, D. M.·Buonomo, S.·Di Virgilio, M.·Neumann, T.·Pavri, R.
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Abstract

The mammalian DNA replication timing (RT) program is crucial for the proper functioning and integrity of the genome. The best-known mechanism for controlling RT is the suppression of late origins of replication in heterochromatin by RIF1. Here, we report that in antigen-activated B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin, regulates early origin firing and promotes early replication. RIF1 has a minor role in gene expression and genome organization in B cells. Furthermore, we find that RIF1 functions in a complementary and non-epistatic manner with minichromosome maintenance (MCM) proteins to establish early RT signatures genome-wide and, specifically, to ensure the early replication of highly transcribed genes. These findings reveal new layers of regulation within the B cell RT program, driven by the coordinated activity of RIF1 and MCM proteins.

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Malzl, D., Peycheva, M., Rahjouei, A., Gnan, S., Klein, K., Nazarova, M., Schoeberl, U. E., Gilbert, D. M., Buonomo, S., Di Virgilio, M., Neumann, T., Pavri, R.. 2023-03-31. RIF1 regulates replication origin activity and early replication timing in B cells. https://doi.org/10.1101/2023.03.31.535086

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