Rif1 functions in a tissue-specific manner to control replication timing through its PP1-binding motif

Armstrong, Robin L.; Das, Souradip; Hill, Christina A.; Duronio, Robert J.; Nordman, Jared

doi:10.1101/870451

Cited by 4 publications

(12 citation statements)

References 63 publications

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“…The high level of similarity is particularly noteworthy in the case of the early RT profiles, given that the flow sorting gate for early replicating nuclei in the endocycle had to be adjusted to minimize contamination from late replicating mitotic nuclei ( Fig 1C ). This overall conservation of the RT program in the endocycle is consistent with a recent study in Drosophila follicle cells which found no regions of differential RT between mitotic and endocycling cells [ 78 ]. Additionally, the global maintenance of RT in the two types of cell cycles in maize roots suggests that the process of re-establishing the RT program must be similar in both.…”

Section: Discussionsupporting

confidence: 91%

Comparing DNA replication programs reveals large timing shifts at centromeres of endocycling cells in maize roots

Wear

Song²,

Zynda³

et al. 2020

PLoS Genet

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Plant cells undergo two types of cell cycles–the mitotic cycle in which DNA replication is coupled to mitosis, and the endocycle in which DNA replication occurs in the absence of cell division. To investigate DNA replication programs in these two types of cell cycles, we pulse labeled intact root tips of maize ( Zea mays ) with 5-ethynyl-2’-deoxyuridine (EdU) and used flow sorting of nuclei to examine DNA replication timing (RT) during the transition from a mitotic cycle to an endocycle. Comparison of the sequence-based RT profiles showed that most regions of the maize genome replicate at the same time during S phase in mitotic and endocycling cells, despite the need to replicate twice as much DNA in the endocycle and the fact that endocycling is typically associated with cell differentiation. However, regions collectively corresponding to 2% of the genome displayed significant changes in timing between the two types of cell cycles. The majority of these regions are small with a median size of 135 kb, shift to a later RT in the endocycle, and are enriched for genes expressed in the root tip. We found larger regions that shifted RT in centromeres of seven of the ten maize chromosomes. These regions covered the majority of the previously defined functional centromere, which ranged between 1 and 2 Mb in size in the reference genome. They replicate mainly during mid S phase in mitotic cells but primarily in late S phase of the endocycle. In contrast, the immediately adjacent pericentromere sequences are primarily late replicating in both cell cycles. Analysis of CENH3 enrichment levels in 8C vs 2C nuclei suggested that there is only a partial replacement of CENH3 nucleosomes after endocycle replication is complete. The shift to later replication of centromeres and possible reduction in CENH3 enrichment after endocycle replication is consistent with a hypothesis that centromeres are inactivated when their function is no longer needed.

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Section: Discussionsupporting

confidence: 91%

Comparing DNA replication programs reveals large timing shifts at centromeres of endocycling cells in maize roots

Wear

Song²,

Zynda³

et al. 2020

PLoS Genet

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“…Late in the S phase, higher CDK—and likely DDK—concentration causes Rif1 inhibition, which results in origin derepression through pre-RC activation [ 31 ]. For polytene chromosomes, the influence of Rif1 on replication timing has been analyzed in detail only for the annotated part of the genome: euchromatin arms and the part of heterochromatin devoid of satellite DNA [ 27 , 65 ]. It has been concluded that Rif1 action is SUUR-dependent and is implemented through the impact on the speed or stability of replication forks [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…These data indicate the existence of at least two mechanisms of Rif1 action, both requiring the interaction of Rif1 with PP1 phosphatase [ 27 , 31 ]. Of note, a mutation in the Rif1 gene has an opposite effect on some eu- and heterochromatin regions [ 65 ].…”

Section: Introductionmentioning

confidence: 99%

“…Drosophila SuUR and Rif1 mutants are completely viable [ 5 , 27 , 31 ]. Recent research into the impact of Rif1 on replication timing in ovarian follicular cells before and after the cells enter the endocycle as well as in diploid cells of larval imaginal discs showed that the removal of functional Rif1 affects only a small fraction of the genome, and this fraction varies in different tissues [ 65 ]. It is important to emphasize that in ref.…”

Section: Introductionmentioning

confidence: 99%

“…It is important to emphasize that in ref. [ 65 ], the effect of Rif1 on satellite replication timing was not investigated.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Mutations in the Drosophila melanogaster Rif1 Gene on the Replication and Underreplication of Pericentromeric Heterochromatin in Salivary Gland Polytene Chromosomes

Колесникова

Kolodyazhnaya

Pokholkova

et al. 2020

Cells

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In Drosophila salivary gland polytene chromosomes, a substantial portion of heterochromatin is underreplicated. The combination of mutations SuURES and Su(var)3-906 results in the polytenization of a substantial fraction of unique and moderately repeated sequences but has almost no effect on satellite DNA replication. The Rap1 interacting factor 1 (Rif) protein is a conserved regulator of replication timing, and in Drosophila, it affects underreplication in polytene chromosomes. We compared the morphology of pericentromeric regions and labeling patterns of in situ hybridization of heterochromatin-specific DNA probes between wild-type salivary gland polytene chromosomes and the chromosomes of Rif1 mutants and SuUR Su(var)3-906 double mutants. We show that, despite general similarities, heterochromatin zones exist that are polytenized only in the Rif1 mutants, and that there are zones that are under specific control of Su(var)3-9. In the Rif1 mutants, we found additional polytenization of the largest blocks of satellite DNA (in particular, satellite 1.688 of chromosome X and simple satellites in chromosomes X and 4) as well as partial polytenization of chromosome Y. Data on pulsed incorporation of 5-ethynyl-2′-deoxyuridine (EdU) into polytene chromosomes indicated that in the Rif1 mutants, just as in the wild type, most of the heterochromatin becomes replicated during the late S phase. Nevertheless, a significantly increased number of heterochromatin replicons was noted. These results suggest that Rif1 regulates the activation probability of heterochromatic origins in the satellite DNA region.

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Temporal control of late replication and coordination of origin firing by self-stabilizing Rif1-PP1 hubs in Drosophila

Cho

Seller

O’Farrell

2022

Preprint

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In the metazoan S phase, coordinated firing of clusters of origins replicates different parts of the genome in a temporal program. Despite advances, neither the mechanism controlling timing nor that coordinating firing of multiple origins is fully understood. Rif1, an evolutionarily conserved inhibitor of DNA replication, recruits protein phosphatase 1 (PP1) and counteracts firing of origins by S-phase kinases. During the mid-blastula transition (MBT) in Drosophila embryos, Rif1 forms subnuclear hubs at each of the large blocks of satellite sequences and delays their replication. Each Rif1 hub disperses abruptly just prior to the replication of the associated satellite sequences. Here, we show that the level of activity of the S-phase kinase, DDK, accelerated this dispersal program, and that the level of Rif1-recruited PP1 retarded it. Further, Rif1-recruited PP1 supported chromatin association of nearby Rif1. This influence of nearby Rif1 can create a community effect counteracting kinase-induced dissociation such that an entire hub of Rif1 undergoes switch-like dispersal at characteristic times that shift in response to the balance of Rif1-PP1 and DDK activities. We propose a model in which the spatiotemporal program of late replication in the MBT embryo is controlled by self-stabilizing Rif1-PP1 hubs, whose abrupt dispersal synchronizes firing of associated late origins.

show abstract

Rif1 functions in a tissue-specific manner to control replication timing through its PP1-binding motif

Cited by 4 publications

References 63 publications

Comparing DNA replication programs reveals large timing shifts at centromeres of endocycling cells in maize roots

Comparing DNA replication programs reveals large timing shifts at centromeres of endocycling cells in maize roots

Effects of Mutations in the Drosophila melanogaster Rif1 Gene on the Replication and Underreplication of Pericentromeric Heterochromatin in Salivary Gland Polytene Chromosomes

Temporal control of late replication and coordination of origin firing by self-stabilizing Rif1-PP1 hubs in Drosophila

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