Telomere-binding protein Taz1 controls global replication timing through its localization near late replication origins in fission yeast

Tazumi, Atsutoshi; Fukuura, Masayoshi; Nakato, Ryuichiro; Kishimoto, Ami; Takenaka, Tomokazu; Ogawa, Shiho; Song, Ji Hoon; Takahashi, Tatsuro; Nakagawa, Takuro; Shirahige, Katsuhiko; Masukata, Hisao

doi:10.1101/gad.194282.112

Cited by 70 publications

(96 citation statements)

References 55 publications

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“…2 A and B). These repeats were previously identified in studies mapping the chromosomal associations of the protein Taz1 (homolog of mammalian TRF1/2), showing Taz1 physically interacts with the elements at their endogenous locations (29,30). Consistently, in the mating-type region, Taz1 was required for the boundary effects of GGTTA-containing elements, specifically (Fig.…”

Section: Resultssupporting

confidence: 48%

“…At their endogenous locations the five STAR elements are close to origins of replication that fire late in S phase and whose late activation depends on both Taz1 and Rif1 (29,35). In total, 26 Taz1-dependent late/dormant origins were identified by Tazumi et al (29) at internal locations in chromosome arms including ori2100 (associated with STAR2), ori1097 (associated with STAR3), ori1176 (associated with STAR4), and ori2100 (associated with STAR5).…”

Section: Ir -R + Ir -R δ S T a R 1 S T A R 2 S T A R 5 S T A R 4 ( S mentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 48%

Section: Ir -R + Ir -R δ S T a R 1 S T A R 2 S T A R 5 S T A R 4 ( S 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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“…Late firing of Taz1-affected origins requires telomere-associated Rif1, which also has been implicated in DNA repair (37,38). However, Rif1 binds only a subset of Taz1-associated late origins (11,38,39), and it is conceivable that Shelterin-mediated telomeric association of these origins allows Rif1 acquisition to promote proper replication and DNA repair. In other words, Taz1-bound late origins in telomeric and arm regions might be controlled in a shared nuclear compartment.…”

Section: Discussionmentioning

confidence: 99%

“…1F and Fig. S2C) (11). The specific association of selected chromosome regions containing origins with the nuclear periphery in sap1-1 cells suggested a possible connection between DNA replication activity and genome reorganization.…”

Section: Nuclear Peripheral Association Of Regions Containing Replicamentioning

confidence: 99%

“…We find that several chromosomal arm regions associate specifically with telomeres in the sap1 mutant. These interaction regions are generally adjacent to replication origins bound by Taz1 (11,12), a counterpart of human TRF1/2 and a component of the Shelterin complex involved in telomeric end protection (13)(14)(15) and facilitation of proper replication of telomeres (16). Interestingly, Shelterin components are required to promote contacts between telomeres and chromosomal arm regions.…”

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confidence: 99%

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Shelterin components mediate genome reorganization in response to replication stress

Mizuguchi

Taneja

Matsuda

et al. 2017

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

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The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication, and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here, we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability and display extensive changes in genome organization. Chromosomal regions such as subtelomeres that show defects in replication progression associate with the nuclear envelope in sap1 mutant cells. Moreover, highresolution, genome-wide chromosome conformation capture (Hi-C) analysis revealed prominent contacts between telomeres and chromosomal arm regions containing replication origins proximal to binding sites for Taz1, a component of the Shelterin telomere protection complex. Strikingly, we find that Shelterin components are required for interactions between Taz1-associated chromosomal arm regions and telomeres. These analyses reveal an unexpected role for Shelterin components in genome reorganization in cells experiencing replication stress, with important implications for understanding the mechanisms governing replication and genome stability.T he 3D organization of the eukaryotic genome creates specialized microenvironments that play important roles in various nuclear processes (1). In addition to regulation of gene expression, proper execution of the DNA replication program and DNA damage repair also involve dynamic organization of the genome (2, 3). Indeed, computational analyses indicate spatial segregation of replication origins based on their timing of firing during S-phase (4), suggesting that besides local chromatin structure, the 3D organization of chromosomes is an important contributing factor in the spatiotemporal control of replication (5, 6). Despite important advances, understanding the connections between diverse chromosomal events and genome organization remains an important challenge.The complexities of genome organization have been studied in several model organisms, including the fission yeast Schizosaccharomyces pombe, for which the 3D organization has been explored at high resolution (7,8). This simple eukaryote contains the basic chromosomal elements of more complex systems, including partitioning of the genome into euchromatin and heterochromatin domains. The S. pombe genome conforms to a Rabl organization pattern in which centromere clusters and telomere clusters are anchored at opposing sides of the nuclear periphery (9, 10). In addition, two key elements shape genome architecture: cohesin-dependent locally crumpled 50-to 100-kb repeating elements called "globules" on chromosome arms and the constraints imposed by the compaction of the chromatin fiber by heterochromatin domains such as at pericentromeric regions (8). The relatively small size of the S. pombe genome combined with the conserved genome...

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Regulation of the Initiation of DNA Replication upon DNA Damage in Eukaryotes

Köhler

Ferreira

Pfander

et al. 2016

The Initiation of DNA Replication in Eukaryotes

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Cycling cells must ensure homeostasis of the genetic information during repeated chromosome replication-segregation cycles. To guarantee genome stability in normal and DNA damage conditions the initiation of DNA replication in eukaryotes is regulated by the cell cycle machinery and the intra S-phase checkpoint (ISC). The cell cycle kinases CDK and DDK induce initiation specifically in S phase, and the ISC inhibits both kinase pathways, suppressing initiation upon DNA damage and replisome stalling to prevent the replication machinery from having to copy damaged DNA templates. Despite this ISC-mediated inhibition, dormant origins are allowed to fire in genomic regions that are actively engaged in replication when the DNA damage occurs. Forks from dormant origins can rescue replisomes that have stalled at DNA lesions, helping to ensure that no part of these replicating regions is left unreplicated in DNA damage conditions. This replisome rescue also helps prevent stalled and collapsed forks from causing genome rearrangements. In higher eukaryotes, these principles of regulating initiation upon DNA damage must be implemented into a particularly complex temporal regulation programme of genome replication. Molecular details of how the ISC, which poses an important barrier against tumour formation, achieves the regulation of initiation upon DNA damage is only beginning to emerge

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Telomere-binding protein Taz1 controls global replication timing through its localization near late replication origins in fission yeast

Cited by 70 publications

References 55 publications

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

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

Shelterin components mediate genome reorganization in response to replication stress

Regulation of the Initiation of DNA Replication upon DNA Damage in Eukaryotes

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