Modeling genome‐wide replication kinetics reveals a mechanism for regulation of replication timing

Yang, Scott Cheng‐Hsin; Rhind, Nick; Bechhoefer, John

doi:10.1038/msb.2010.61

Cited by 120 publications

(244 citation statements)

References 43 publications

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“…It supports a model Yang et al 2010) in which replication timing is determined by the stochastic firing of origins that compete for rate-limiting activators ( Fig. 4; Patel et al 2008;Mantiero et al 2011;Tanaka et al 2011).…”

Section: Discussionsupporting

confidence: 80%

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Replication timing is regulated by the number of MCMs loaded at origins

et al. 2015

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Replication timing is a crucial aspect of genome regulation that is strongly correlated with chromatin structure, gene expression, DNA repair, and genome evolution. Replication timing is determined by the timing of replication origin firing, which involves activation of MCM helicase complexes loaded at replication origins. Nonetheless, how the timing of such origin firing is regulated remains mysterious. Here, we show that the number of MCMs loaded at origins regulates replication timing. We show for the first time in vivo that multiple MCMs are loaded at origins. Because early origins have more MCMs loaded, they are, on average, more likely to fire early in S phase. Our results provide a mechanistic explanation for the observed heterogeneity in origin firing and help to explain how defined replication timing profiles emerge from stochastic origin firing. These results establish a framework in which further mechanistic studies on replication timing, such as the strong effect of heterochromatin, can be pursued.

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Section: Discussionsupporting

confidence: 80%

“…1B; Yang et al 2010). In our mathematical model of replication timing, n is the parameter that describes the firing-time distribution of origins.…”

Section: Resultsmentioning

confidence: 99%

Replication timing is regulated by the number of MCMs loaded at origins

et al. 2015

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“…Figure 8 shows a model in which these two possibilities are diagramed in two example regions, the middle of a chromosome arm, and a pericentromere. While not all initiation regions are associated with peaks in a population average replication timing profile, sharp peaks reflect a population preference for initiation in that region (Yang et al, 2010;Hyrien, 2016). The presence of some relatively sharp peaks in mid S suggests these may be initiation zones ( Figure 8B).…”

Section: Models For Maize Dna Replication Timingmentioning

confidence: 99%

Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips

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Song²,

Zynda³

et al. 2017

Plant Cell

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All plants and animals must replicate their DNA, using a regulated process to ensure that their genomes are completely and accurately replicated. DNA replication timing programs have been extensively studied in yeast and animal systems, but much less is known about the replication programs of plants. We report a novel adaptation of the "Repli-seq" assay for use in intact root tips of maize (Zea mays) that includes several different cell lineages and present whole-genome replication timing profiles from cells in early, mid, and late S phase of the mitotic cell cycle. Maize root tips have a complex replication timing program, including regions of distinct early, mid, and late S replication that each constitute between 20 and 24% of the genome, as well as other loci corresponding to ;32% of the genome that exhibit replication activity in two different time windows. Analyses of genomic, transcriptional, and chromatin features of the euchromatic portion of the maize genome provide evidence for a gradient of early replicating, open chromatin that transitions gradually to less open and less transcriptionally active chromatin replicating in mid S phase. Our genomic level analysis also demonstrated that the centromere core replicates in mid S, before heavily compacted classical heterochromatin, including pericentromeres and knobs, which replicate during late S phase.

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“…These two parameters may be generalized to earlier ROs being more efficient and the converse. [25][26] Timing and efficiency can also describe the probability of origin firing -early timing reflects a high chance of RO activation early in the S phase, and high efficiency depicts probability of consistent firing across the entire replication process. Hence it has been suggested that timing and efficiency may be dictated by some fundamental mechanisms.…”

Section: Origin Competence Efficiency and Dormancymentioning

confidence: 99%