A diffusion model for the coordination of DNA replication in Schizosaccharomyces pombe

Pichugina, Tatyana; Sugawara, Takeshi; Kaykov, Atanas; Schierding, William; Masuda, Kenta; Uewaki, Jun-ichi; Grand, Ralph S.; Allison, Jane R.; Martienssen, Robert A.; Nurse, Paul; Ueno, Masaru; O’Sullivan, Justin M.

doi:10.1038/srep18757

Cited by 16 publications

(28 citation statements)

References 34 publications

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“…Heterochromatin is characterized by the strong suppression of foreign gene expression and enriched in H3K9me2 and H3K9me3. As in metazoans, heterochromatin in S. pombe is localized at the periphery of the nucleus or nucleolus as predicted from polymer models (Pichugina et al ., ). It was commonly believed that silent heterochromatin is highly condensed and excludes transcription factors from accessing DNA, as in metazoans.…”

Section: Higher‐ordered Structures Of Chromatin Domainsmentioning

confidence: 97%

“…Direct measurements of physicochemical properties of chromosomes also provide insights into the nuclear organization of the chromosomes. Polymer models of chromosomes have also been used for predicting biologically relevant properties of chromosomes (Tanizawa et al ., ; Grand et al ., ; Gong et al ., 2015; Pichugina et al ., ). Combinations of these techniques will provide new insights into the temporal and spatial organization of the nucleus during biological processes.…”

Section: Perspectivesmentioning

confidence: 97%

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Spatial organization of theSchizosaccharomyces pombegenome within the nucleus

Matsuda

Asakawa

Haraguchi

et al. 2016

Yeast

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The fission yeast Schizosaccharomyces pombe is a useful experimental system for studying the organization of chromosomes within the cell nucleus. S. pombe has a small genome that is organized into three chromosomes. The small size of the genome and the small number of chromosomes are advantageous for cytological and genomewide studies of chromosomes; however, the small size of the nucleus impedes microscopic observations owing to limits in spatial resolution during imaging. Recent advances in microscopy, such as super-resolution microscopy, have greatly expanded the use of S. pombe as a model organism in a wide range of studies. In addition, biochemical studies, such as chromatin immunoprecipitation and chromosome conformation capture, have provided complementary approaches. Here, we review the spatial organization of the S. pombe genome as determined by a combination of cytological and biochemical studies.

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Section: Higher‐ordered Structures Of Chromatin Domainsmentioning

confidence: 97%

Section: Perspectivesmentioning

confidence: 97%

Spatial organization of theSchizosaccharomyces pombegenome within the nucleus

Matsuda

Asakawa

Haraguchi

et al. 2016

Yeast

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“…The spatio-temporal model simulates DNA replication at a whole-genome level and is tailored to the case of fission yeast, exploiting recent three-dimensional genome structures derived by chromosome conformation capture experiments [43,57]. A graphical summary of the model is given in Fig.…”

Section: A Stochastic Three-dimensional Model Of Dna Replicationmentioning

confidence: 99%

“…In budding yeast nuclei, early firing origins were found to be clustered [42]. A recent study in fission yeast identified a gradient of origin efficiency centered on the spindle pole body (SPB), suggesting a diffusion-based mechanism coordinating DNA replication [43].…”

Section: Introductionmentioning

confidence: 99%

A stochastic hybrid model of DNA replication incorporating 3D protein mobility dynamics

Windhager

Paine

Nathanailidou

et al. 2019

Preprint

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DNA replication is a complex process that ensures the maintenance of genetic information. Recently, advancements in chromatin conformation capture techniques have enabled the modeling of DNA replication as a spatio-temporal process. Here, we present a stochastic hybrid model for DNA replication that incorporates protein mobility dynamics and 3D chromatin structure. Performing simulations for three model variations and a broad range of parameter values, we collected about 300,000 in silico replication profiles for fission yeast and conducted a parameter sensitivity analysis. We find that the number of firing factors initiating replication is rate-limiting and dominates the time until completion of DNA replication. In support of recent work, we also find that explicitly modeling the recruitment of firing factors by the spindle pole body (SPB) best recapitulates published origin efficiencies, and independently validate these findings in vivo. Accounting for probabilistic effects in molecular interactions, we further investigated the replication kinetics inherent to the model and were able to capture known properties of DNA replication. Importantly, we confirm earlier observations that, without further assumptions, the characteristic shape of a function commonly used to describe replication kinetics arises from a rate-limiting number of firing factors in conjunction with their recycling upon replication fork collision. While the model faithfully recapitulates global spatial patterns of replication initiation, additional analysis of spatial concurrence and competition suggests that a uniform binding probability is too simplistic to capture local neighborhood effects in origin firing. In summary, our model provides a framework to realistically simulate DNA replication for a complete eukaryotic genome, and to investigate the relationship between three-dimensional chromatin conformation and DNA replication timing.Recent advancements in chromosome conformation capture techniques (e.g., 3C, Hi-C) have enabled the determination of DNA structure and nuclear organization. As a consequence, studies on various organisms have observed that DNA replication timing is highly correlated with chromatin folding and global nuclear architecture [34][35][36]. In mammalian cells, chromatin conformation maps agree with replication timing profiles

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“…A proposed mechanism for epigenetic inheritance is that the association of H3K9 methyltransferases with replicative polymerases would facilitate the modification of newly deposited nucleosomes with marks specific for the replicated region, as might also be the case for other modifications (19)(20)(21)(22). Such associations have indicated that replication control could be important for the chromatin domain organization of chromosomes by restricting the spreading of modifying enzymes to specific regions, either in 2D along the chromatin fiber or perhaps in 3D, through the coregulation of replication origins or forks occupying a common subnuclear compartment (23).…”

mentioning

confidence: 99%

Establishment of expression-state boundaries by Rif1 and Taz1 in fission yeast

Toteva

Mason

Kanoh

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The Shelterin component Rif1 has emerged as a global regulator of the replication-timing program in all eukaryotes examined to date, possibly by modulating the 3D-organization of the genome. In fission yeast a second Shelterin component, Taz1, might share similar functions. Here, we identified unexpected properties for Rif1 and Taz1 by conducting high-throughput genetic screens designed to identify cis-and transacting factors capable of creating heterochromatin-euchromatin boundaries in fission yeast. The preponderance of cis-acting elements identified in the screens originated from genomic loci bound by Taz1 and associated with origins of replication whose firing is repressed by Taz1 and Rif1. Boundary formation and gene silencing by these elements required Taz1 and Rif1 and coincided with altered replication timing in the region. Thus, small chromosomal elements sensitive to Taz1 and Rif1 (STAR) could simultaneously regulate gene expression and DNA replication over a large domain, at the edge of which they established a heterochromatin-euchromatin boundary. Taz1, Rif1, and Rif1-associated protein phosphatases Sds21 and Dis2 were each sufficient to establish a boundary when tethered to DNA. Moreover, efficient boundary formation required the amino-terminal domain of the Mcm4 replicative helicase onto which the antagonistic activities of the replication-promoting Dbf4-dependent kinase and Rif1-recruited phosphatases are believed to converge to control replication origin firing. Altogether these observations provide an insight into a coordinated control of DNA replication and organization of the genome into expression domains.heterochromatin | chromatin boundaries | DNA replication program | gene silencing | fission yeast

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A diffusion model for the coordination of DNA replication in Schizosaccharomyces pombe

Cited by 16 publications

References 34 publications

Spatial organization of theSchizosaccharomyces pombegenome within the nucleus

Spatial organization of theSchizosaccharomyces pombegenome within the nucleus

A stochastic hybrid model of DNA replication incorporating 3D protein mobility dynamics

Establishment of expression-state boundaries by Rif1 and Taz1 in fission yeast

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