Telomere-to-telomere human DNA replication timing profiles

Massey, Dashiell J.; Koren, Amnon

doi:10.1038/s41598-022-13638-8

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…In other words, there is a centromere that can be recognised by ORC, which contains a region that can play the role of an ARS (Popova et al, 2018;Massey & Koren, 2022). Comparing our results with those of previous studies, it is expected that the centromeric regions of P. tricornutum do not contain ARSs and do not exhibit non-replicative functions (Popova et al, 2018;Massey & Koren, 2022).…”

Section: Discussionsupporting

confidence: 77%

“…Interestingly, Drosophila and mammalian ORCs interact with centromeric regions, whereas yeast ORCs do not (Popova et al, 2018). Furthermore, a centromeric replication origin was reported to exist in the mammalian centromere (Pelletier et al, 1999;Massey & Koren, 2022). In other words, there is a centromere that can be recognised by ORC, which contains a region that can play the role of an ARS (Popova et al, 2018;Massey & Koren, 2022).…”

Section: Discussionmentioning

confidence: 99%

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Genome-wide mapping of autonomously replicating sequences in the marine diatomPhaeodactylum tricornutum

Yun,

Yoneda,

Sugasawa

et al. 2024

Preprint

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Autonomously replicating sequences (ARSs) are important accessories in episomal vectors that allow them to be replicated and stably maintained within transformants. Despite their importance, no information on ARSs in diatoms have been reported. Therefore, we attempted to identify ARS candidates in the model diatom,Phaeodactylum tricornutum, via chromatin immunoprecipitation sequencing. In this study, subunits of the origin recognition complex (ORC), ORC2 and ORC4, were used to screen for ARS candidates. ORC2 and ORC4 bound to 355 sites on theP. tricornutumgenome, of which 69 were constantly screened after multiple attempts. The screened ARS candidates had an AT-richness of approximately 50% (44.39–52.92%) and did not have conserved sequences. In addition, ARS candidates were distributed randomly but had a dense distribution pattern at several sites. Their positions tended to overlap with those of the genetic region (73.91%). Compared to the ARSs of several other eukaryotic organisms, the characteristics of the screened ARS candidates are complex. Thus, our findings suggest that the diatom has a distinct and unique native ARSs.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Genome-wide mapping of autonomously replicating sequences in the marine diatomPhaeodactylum tricornutum

Yun,

Yoneda,

Sugasawa

et al. 2024

Preprint

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“…The availability of complete human genome sequences, development in long-read next-generation sequencing, and powerful algorithms have enabled the mapping of replication timing of human centromeres in individual chromosomes where most of the regions replicate later in the S phase [ 26 , 46 ]. We compared the replication timing of centromeric repeats from repli-FISH with these results and found a similar pattern of S II and S III replicating centromeric repeats.…”

Section: Conclusion/discussionmentioning

confidence: 99%

Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells

Pradhan,

Lozoya,

Prorok

et al. 2024

Genes

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DNA replication is a fundamental process ensuring the maintenance of the genome each time cells divide. This is particularly relevant early in development when cells divide profusely, later giving rise to entire organs. Here, we analyze and compare the genome replication progression in human embryonic stem cells, induced pluripotent stem cells, and differentiated cells. Using single-cell microscopic approaches, we map the spatio-temporal genome replication as a function of chromatin marks/compaction level. Furthermore, we mapped the replication timing of subchromosomal tandem repeat regions and interspersed repeat sequence elements. Albeit the majority of these genomic repeats did not change their replication timing from pluripotent to differentiated cells, we found developmental changes in the replication timing of rDNA repeats. Comparing single-cell super-resolution microscopic data with data from genome-wide sequencing approaches showed comparable numbers of replicons and large overlap in origins numbers and genomic location among developmental states with a generally higher origin variability in pluripotent cells. Using ratiometric analysis of incorporated nucleotides normalized per replisome in single cells, we uncovered differences in fork speed throughout the S phase in pluripotent cells but not in somatic cells. Altogether, our data define similarities and differences on the replication program and characteristics in human cells at different developmental states.

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“…One of the distinctive features of human embryonic cells is their internal nuclear centromere localization (Wiblin et al, 2005). Although mechanisms governing cell type-speci c pan-centromeric replication timing are unknown, they can be associated with spatial organization of nuclei (Massey and Koren, 2022). Analysis of centromere composition in pluripotent cells revealed reduced centromeric chromatin size due to weaker recruitment of the centromere-speci c histone CENP-A during the shortened G1 phase (Milagre et al, 2020).…”

Section: Moderate Replication Stress Severely Delays Mitotic Entry In...mentioning

confidence: 99%

Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells

Kislova,

Zheglo,

Pozhitnova

et al. 2023

Chromosome Res

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Substantial background level of replication stress is a feature of embryonic and induced pluripotent stem cells (iPSCs), which can predispose to numerical and structural chromosomal instability, including recurrent aberrations of Chromosome 12. In differentiated cells, replication stress-sensitive genomic regions, including common fragile sites, are widely mapped through mitotic chromosome break induction by mild Aphidicolin treatment, an inhibitor of replicative polymerases. IPSCs exhibit lower apoptotic threshold and higher repair capacity hindering fragile site mapping. Caffeine potentiates genotoxic effects and abrogates G2/M checkpoint delay induced by chemical and physical mutagens. Using 5ethynyl-2'-deoxyuridine (EdU) for replication labeling, we characterized the mitotic entry dynamics of asynchronous iPSCs exposed to Aphidicolin and/or Caffeine. Under the adjusted timing of replication stress exposure accounting revealed cell cycle delay, higher metaphase chromosome breakage rate was observed in iPSCs compared to primary lymphocytes. Using differential chromosome staining and subsequent locus-speci c uorescent in situ hybridization, we mapped the FRA12L fragile site spanning the large neuronal ANKS1B gene at 12q23.1, which may contribute to recurrent Chromosome 12 missegregation and rearrangements in iPSCs. Publicly available data on the ANKS1B genetic alterations and their possible functional impact are reviewed. Our study provides the rst evidence of common fragile site induction in iPSCs and reveals potential somatic instability of a clinically relevant gene during early human development and in vitro cell expansion.

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Telomere-to-telomere human DNA replication timing profiles

Cited by 8 publications

References 34 publications

Genome-wide mapping of autonomously replicating sequences in the marine diatomPhaeodactylum tricornutum

Genome-wide mapping of autonomously replicating sequences in the marine diatomPhaeodactylum tricornutum

Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells

Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells

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