DNA replication timing: Coordinating genome stability with genome regulation on the X chromosome and beyond

Abstract Motivation Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges. Results We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale. Availability and Implementation TIGER is available at https://github.com/TheKorenLab/TIGER. Supplementary information Supplementary data are available at Bioinformatics online

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The Protective Role of Dormant Origins in Response to Replicative Stress

International Journal of Molecular Sciences ◽

10.3390/ijms19113569 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3569 ◽

Cited By ~ 11

Author(s):

Lilas Courtot ◽

Jean-Sébastien Hoffmann ◽

Valérie Bergoglio

Keyword(s):

Dna Replication ◽

Mammalian Cells ◽

Genome Stability ◽

Replication Timing ◽

Protective Role ◽

Entire Genome ◽

Replicative Stress ◽

A Cell ◽

The Many

Genome stability requires tight regulation of DNA replication to ensure that the entire genome of the cell is duplicated once and only once per cell cycle. In mammalian cells, origin activation is controlled in space and time by a cell-specific and robust program called replication timing. About 100,000 potential replication origins form on the chromatin in the gap 1 (G1) phase but only 20–30% of them are active during the DNA replication of a given cell in the synthesis (S) phase. When the progress of replication forks is slowed by exogenous or endogenous impediments, the cell must activate some of the inactive or “dormant” origins to complete replication on time. Thus, the many origins that may be activated are probably key to protect the genome against replication stress. This review aims to discuss the role of these dormant origins as safeguards of the human genome during replicative stress.

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Asymmetrical deposition and modification of histone H3 variants are essential for zygote development

Life Science Alliance ◽

10.26508/lsa.202101102 ◽

2021 ◽

Vol 4 (8) ◽

pp. e202101102

Author(s):

Machika Kawamura ◽

Satoshi Funaya ◽

Kenta Sugie ◽

Masataka G Suzuki ◽

Fugaku Aoki

Keyword(s):

Dna Replication ◽

Mrna Expression ◽

Detrimental Effect ◽

Histone H3 ◽

Replication Timing ◽

Male And Female ◽

Zygote Development ◽

The One ◽

Dna Replication Timing ◽

Incorporation Efficiency

The pericentromeric heterochromatin of one-cell embryos forms a unique, ring-like structure around the nucleolar precursor body, which is absent in somatic cells. Here, we found that the histone H3 variants H3.1 and/or H3.2 (H3.1/H3.2) were localized asymmetrically between the male and female perinucleolar regions of the one-cell embryos; moreover, asymmetrical histone localization influenced DNA replication timing. The nuclear deposition of H3.1/3.2 in one-cell embryos was low relative to other preimplantation stages because of reduced H3.1/3.2 mRNA expression and incorporation efficiency. The forced incorporation of H3.1/3.2 into the pronuclei of one-cell embryos triggered a delay in DNA replication, leading to developmental failure. Methylation of lysine residue 27 (H3K27me3) of the deposited H3.1/3.2 in the paternal perinucleolar region caused this delay in DNA replication. These results suggest that reduced H3.1/3.2 in the paternal perinucleolar region is essential for controlled DNA replication and preimplantation development. The nuclear deposition of H3.1/3.2 is presumably maintained at a low level to avoid the detrimental effect of K27me3 methylation on DNA replication in the paternal perinucleolar region.

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