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Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication [IP-seq]

GSE293196 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/10/27 Platform GPL24676
Summary
Replication origins in human cells form clusters ranging from tens to hundreds of kilobases called initiation zones (IZs), typically located in intergenic regions between active genes. On a larger megabase scale, chromosomes replicate in a temporally defined replication timing (RT) pattern, where euchromatic regions replicate early, and heterochromatic regions replicate late. Although the stochastic model of IZ firing with a temporally regulated limiting factor can explain RT formation, this limiting factor in human cells remains unclear. To investigate the relationship between IZ and RT, we mapped the temporal firing pattern of IZs and examined the genome-wide distributions of replication licensing and firing factors in human cells. We identified TRESLIN-MTBP as the key limiting firing factor for replication initiation. Its loading onto phosphorylated MCM2–7 double hexamer (MCM-DH) is controlled by the opposing phosphorylation events on MCM-DH by Dbf4-dependent kinase and RIF1-Protein Phosphatase 1, which ultimately determine IZs and establish RT.
Published in
Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication
Zhu X, Bektash A, Hatoyama Y et al. · Nature communications 2025 · PMID 41331242 · doi:10.1038/s41467-025-66278-7
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Also filed as BioProject PRJNA1243337 and SRA study SRP574054. Searching any of these in the dataset finder brings you back here.

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