Nature CommunicationsGeneticsPeer-reviewed journal article
RIF1 regulates replication origin activity and early replication timing in B cells
Daniel MalzliD, Mihaela PeychevaiD, Ali RahjoueiiD, Stefano GnaniD, Kyle N. KleiniD, Mariia NazarovaiD, Ursula E. SchoeberliD, David M. GilbertiD, Sara B.C. BuonomoiD, Michela Di VirgilioiD, Tobias NeumanniD, Rushad PavriiD
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.
- Citations
- 12
- FWCI
- 1.07
- Field percentile
- top 25%
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Rif1 functions in a tissue-specific manner to control replication timing through its PP1-binding motif
Robin L. Armstrong, Souradip Das, … Jared T. Nordman·GeneticsPeer-reviewed·Mar 6, 2020
- Zebrafish Rif1 impacts zygotic genome activation, replication timing, and sex determination
E. A. Masser, T. D. Noble, … C. L. Sansam·bioRxiv·Oct 21, 2022
- 2C-RT Quantifies Genome-Wide DNA Replication Perturbations and Redefines RIF1-CDC7 Regulation of Replication Timing
Bruno Urién, Philip Yuk Kuwong, … Bennie B. L. G. Lemmens·bioRxiv·Oct 23, 2026
- Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction
Stefano Gnan, Ilya M. Flyamer, … Sara B.C. Buonomo·Nature CommunicationsPeer-reviewed·May 18, 2021
- Active transcription regulates ORC/MCM distribution whereas replication timing correlates with ORC density in human cells
N. Kirstein, A. Buschle, … A. Schepers·bioRxiv·Sep 23, 2019
- RNA-binding proteins control the G2-M checkpoint of the germinal centre B cell
Fiamma Salerno, Alex J. Whale, … Martin Turner·Science ImmunologyPeer-reviewed·Oct 31, 2025