Shelterin promotes tethering of late replication origins to telomeres for replication‐timing control

Extrachromosomal elements are common early intermediates of gene amplification in vivo and in cell culture. The time at which several extrachromosomal elements replicate was compared with that of the corresponding amplified or unamplified chromosomal sequences. The replication timing analysis employed a retroactive synchrony method in which fluorescence-activated cell sorting was used to obtain cells at different stages of the cell cycle. Extrachromosomally amplified Syrian hamster CAD genes (CAD is an acronym for the single gene which encodes the trifunctional protein which catalyzes the first three steps of uridine biosynthesis) replicated in a narrow window of early S-phase which was approximately the same as that of chromosomally amplified CAD genes. Similarly, extrachromosomally amplified mouse adenosine deaminase genes replicated at a discrete time in early S-phase which approximated the replication time of the unamplified adenosine deaminase gene. In contrast, the multicopy extrachromosomal Epstein-Barr virus genome replicated within a narrow window in late S-phase in latently infected human Rajii cells. The data indicate that localization within a chromosome is not required for the maintenance of replication timing control.

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Genome-wide mapping of human DNA-replication origins: Levels of transcription at ORC1 sites regulate origin selection and replication timing

Genome Research ◽

10.1101/gr.142331.112 ◽

2012 ◽

Vol 23 (1) ◽

pp. 1-11 ◽

Cited By ~ 93

Author(s):

G. I. Dellino ◽

D. Cittaro ◽

R. Piccioni ◽

L. Luzi ◽

S. Banfi ◽

...

Keyword(s):

Dna Replication ◽

Replication Timing ◽

Replication Origins ◽

Human Dna ◽

Genome Wide ◽

Dna Replication Origins

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Rif1 Regulates Initiation Timing of Late Replication Origins throughout the S. cerevisiae Genome

PLoS ONE ◽

10.1371/journal.pone.0098501 ◽

2014 ◽

Vol 9 (5) ◽

pp. e98501 ◽

Cited By ~ 52

Author(s):

Jared M. Peace ◽

Anna Ter-Zakarian ◽

Oscar M. Aparicio

Keyword(s):

Late Replication ◽

Replication Origins

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Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins

10.1101/538363 ◽

2019 ◽

Author(s):

Haiyang Zhang ◽

Meghan V. Petrie ◽

Yiwei He ◽

Jared M. Peace ◽

Irene E. Chiolo ◽

...

Keyword(s):

Dna Replication ◽

Spatial Organization ◽

Nuclear Periphery ◽

Replication Timing ◽

G1 Phase ◽

Replication Origins ◽

Chromosomal Dna ◽

Dna Elements ◽

Functional Dna ◽

High Level

ABSTRACTChromosomal DNA elements are organized into spatial domains within the eukaryotic nucleus. Sites undergoing DNA replication, high-level transcription, and repair of double-strand breaks coalesce into foci, although the significance and mechanisms giving rise to these dynamic structures are poorly understood. InS. cerevisiae, replication origins occupy characteristic subnuclear localizations that anticipate their initiation timing during S phase. Here, we link localization of replication origins in G1 phase with Fkh1 activity, which is required for their early replication timing. Using a Fkh1-dependent origin relocalization assay, we determine that execution of Dbf4-dependent kinase function, including Cdc45 loading, results in dynamic relocalization of a replication origin from the nuclear periphery to the interior in G1 phase. Origin mobility increases substantially with Fkh1-driven relocalization. These findings provide novel molecular insight into the mechanisms that govern dynamics and spatial organization of DNA replication origins and possibly other functional DNA elements.

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Replication dynamics of individual loci in single living cells reveal variation of stochasticity

10.1101/485987 ◽

2018 ◽

Author(s):

Bénédicte Duriez ◽

Sabarinadh Chilaka ◽

Jean-François Bercher ◽

Eslande Hercul ◽

Nicole Boggetto ◽

...

Keyword(s):

Replication Timing ◽

S Phase ◽

Timing Control ◽

Homologous Chromosomes ◽

Stochastic Nature ◽

Time Period ◽

Single Living Cells ◽

Phase Out ◽

Single Living ◽

Eukaryotic Genomes

AbstractEukaryotic genomes are replicated under the control of a highly sophisticated program during the restricted time period corresponding to S-phase. The most widely used replication timing assays, which are performed on populations of millions of cells, suggest that most of the genome is synchronously replicated on homologous chromosomes. We investigated the stochastic nature of this temporal program, by comparing the precise replication times of allelic loci within single vertebrate cells progressing through S-phase at six loci replicated from very early to very late. We show that replication timing is strictly controlled for the three loci replicated in the first half of S-phase. Out of the three loci replicated in the second part of S-phase, two present a significantly more stochastic pattern. Surprisingly, we find that the locus replicated at the very end of S-phase, presents stochasticity similar to those replicated in early S-phase. We suggest that the richness of loci in efficient origins of replication, which decreases from early-to late-replicating regions, may underlie the variation of timing control during S-phase.

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