OriDB: a DNA replication origin database

Nieduszynski, Conrad A.; Hiraga, Shin‐ichiro; Ak, Prashanth; Benham, Craig J.; Donaldson, Anne

doi:10.1093/nar/gkl758

Cited by 165 publications

(207 citation statements)

References 45 publications

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“…This replication pattern indicates that the sites most prone to replication initiation at 37°C in cdc7-1 rif1D are likely to correspond to normally early initiating origins; for example, origins ARS418, ARS428, and ARS432.5 (arrowheads in Fig. 1D; Nieduszynski et al 2007;Siow et al 2012).…”

Section: Resultsmentioning

confidence: 90%

Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex

et al. 2014

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Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.

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Section: Resultsmentioning

confidence: 90%

Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex

et al. 2014

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“…Replication timing profiles allow the analysis of chromosomally active replication origins; however, approximately half of all origins in S. cerevisiae are dormant-that is, they are not normally active in their chromosomal context (Nieduszynski et al 2007). In yeast the activity of these dormant origins can be assayed by their ability to support plasmid replication.…”

Section: Discussionmentioning

confidence: 99%

“…The budding yeast genome is replicated from hundreds of origins (Nieduszynski et al 2007) and metazoan genomes from thousands of origins (Mechali 2010). Failure to activate sufficient or appropriately distributed origins can delay genome replication and may be the underlying cause of some human diseases (Bicknell et al 2011a,b;Guernsey et al 2011;Letessier et al 2011).…”

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confidence: 99%

Conservation of replication timing reveals global and local regulation of replication origin activity

2012

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DNA replication initiates from defined locations called replication origins; some origins are highly active, whereas others are dormant and rarely used. Origins also differ in their activation time, resulting in particular genomic regions replicating at characteristic times and in a defined temporal order. Here we report the comparison of genome replication in four budding yeast species: Saccharomyces cerevisiae, S. paradoxus, S. arboricolus, and S. bayanus. First, we find that the locations of active origins are predominantly conserved between species, whereas dormant origins are poorly conserved. Second, we generated genome-wide replication profiles for each of these species and discovered that the temporal order of genome replication is highly conserved. Therefore, active origins are not only conserved in location, but also in activation time. Only a minority of these conserved origins show differences in activation time between these species. To gain insight as to the mechanisms by which origin activation time is regulated we generated replication profiles for a S. cerevisiae/S. bayanus hybrid strain and find that there are both local and global regulators of origin function.

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“…To identify the chromatin parameters that affect origin properties, we systematically analyzed chromatin structure around all 798 predicted origins in the OriDB database (Nieduszynski et al 2007;Belsky et al 2015) in G1 phase. Origins are typically located within nucleosome depleted regions (NDRs), which are surrounded by well-positioned nucleosomes (Eaton et al 2010).…”

Section: Nucleosome Occupancy Varies Across Origins In G1 and Is Orc-mentioning

confidence: 99%

Nucleosome occupancy as a novel chromatin parameter for replication origin functions

et al. 2016

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Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation.

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OriDB: a DNA replication origin database

Cited by 165 publications

References 45 publications

Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex

Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex

Conservation of replication timing reveals global and local regulation of replication origin activity

Nucleosome occupancy as a novel chromatin parameter for replication origin functions

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