Promoters are key organizers of the duplication of vertebrate genomes

Brossas, Caroline; Duriez, Bénédicte; Valton, Anne‐Laure; Prioleau, Marie‐Noëlle

doi:10.1002/bies.202100141

Cited by 5 publications

(3 citation statements)

References 62 publications

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“…Replication initiates in moderately transcribed regions and is associated with DNase hypersensitive sites. Moreover, genome-wide experiments have bolstered the co-regulation model of replication initiation and transcription [ 43 ]. These are active areas of study, and we hope to learn the mechanistic details in the coming years.…”

Section: Chromatin Signature At the Originsmentioning

confidence: 99%

Chromatin’s Influence on Pre-Replication Complex Assembly and Function

Ahmad,

Chetlangia,

Prasanth

2024

Biology

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In all eukaryotes, the initiation of DNA replication requires a stepwise assembly of factors onto the origins of DNA replication. This is pioneered by the Origin Recognition Complex, which recruits Cdc6. Together, they bring Cdt1, which shepherds MCM2-7 to form the OCCM complex. Sequentially, a second Cdt1-bound hexamer of MCM2-7 is recruited by ORC-Cdc6 to form an MCM double hexamer, which forms a part of the pre-RC. Although the mechanism of ORC binding to DNA varies across eukaryotes, how ORC is recruited to replication origins in human cells remains an area of intense investigation. This review discusses how the chromatin environment influences pre-RC assembly, function, and, eventually, origin activity.

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Section: Chromatin Signature At the Originsmentioning

confidence: 99%

Chromatin’s Influence on Pre-Replication Complex Assembly and Function

Ahmad,

Chetlangia,

Prasanth

2024

Biology

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“…A fourth round of protein recruitment finally sets functional replisomes that initiate replication according to a cell type-specific timing program 12 . This program is regulated at the level of largescale domains 13 by a complex combination of cis-regulatory sequences 14 , trans-acting factors and 3D genome architecture [15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

The balance between ATR and DDK activities controls TopBP1-mediated locking of dormant origins at the pre-IC stage

Koundrioukoff,

Kim,

Alary

et al. 2023

Preprint

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SummaryReplication stress, a major hallmark of cancers, and ensuing genome instability source from impaired progression of replication forks. The first line of defense against fork slowing is compensation, a long-described process that elicits firing of otherwise dormant origins. It remains unclear whether compensation requires activation of the DNA replication checkpoint or passively results from lengthening of the window of time during which dormant origins can fire when fork progression slows, or both. Using molecular DNA combing we show here that a linear relationship ties inter-origin distances to fork speeds, independently of the checkpoint status. We called this line “stressline” and further show that its slope enables precise quantification of the compensation efficiency. Comparison of the slopes in different genetic backgrounds reveals that compensation requires ATR, not CHK1, while TopBP1 and CDC7/DBF4 repress dormant origin activation. These results strongly suggest that TopBP1 locks dormant origins at the pre-IC stage and that ATR and DDK oppose to control the conversion of dormant pre-ICs into functional salvage origins. Both passive and active processes thus contribute to compensation. Moreover, Repli-seq and OK-seq analyses confirm the activating role of ATR and permit development of ATRAP-seq, a new procedure allowing mapping of early constitutive origins.

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“…Large chromosomal domains (replication domains; RDs) replicate at different times during S phase, and this is known as the replication timing (RT) program. Early and late RT are correlated with transcriptionally active and inactive chromatin, respectively (Brossas, Duriez, Valton, & Prioleau, 2021; Marchal, Sima, & Gilbert, 2019; Vouzas & Gilbert, 2021). RDs correspond to structural units of chromosomes called topologically‐associating domains (TADs; Fu, Baris, & Aladjem, 2018; Marchal et al., 2019; Pope et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

Mapping Replication Timing in Single Mammalian Cells

et al. 2022

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Replication timing (RT) is the temporal order in which genomic DNA is replicated during S phase. Early and late replication correlate with transcriptionally active and inactive chromatin compartments, but mechanistic links between large‐scale chromosome structure, transcription, and replication are still enigmatic. A proper RT program is necessary to maintain the global epigenome that defines cell identity, suggesting that RT is critical for epigenome integrity by facilitating the assembly of different types of chromatin at different times during S phase. RT is regulated during development and has been found to be altered in disease. Thus, RT can identify stable epigenetic differences distinguishing cell types, and can be used to help stratify patient outcomes and identify markers of disease. Most methods to profile RT require thousands of S‐phase cells. In cases where cells are rare (e.g., early‐stage embryos or rare primary cell types) or consist of a heterogeneous mixture of cell states (e.g., differentiation intermediates), or when the interest is in determining the degree of stable epigenetic heterogeneity within a population of cells, single‐cell measurements of RT are necessary. We have previously developed single cell Repli‐seq, a method to measure replication timing in single cells using DNA copy number quantification. To date, however, single‐cell Repli‐seq suffers from relatively low throughput and high costs. Here, we describe an improved single‐cell Repli‐seq protocol that uses degenerate oligonucleotide–primed PCR (DOP‐PCR) for uniform whole‐genome amplification and uniquely barcoded primers that permit early pooling of single‐cell samples into a single library preparation. We also provide a bioinformatics platform for analysis of the data. The improved throughput and decreased costs of this method relative to previously published single‐cell Repli‐seq protocols should make it considerably more accessible to a broad range of investigators. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Whole Genome Amplification (WGA) of single cells and sequence library construction. Basic Protocol 2: Deriving and displaying single‐cell replication timing data from whole genome sequencing.

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Promoters are key organizers of the duplication of vertebrate genomes

Cited by 5 publications

References 62 publications

Chromatin’s Influence on Pre-Replication Complex Assembly and Function

Chromatin’s Influence on Pre-Replication Complex Assembly and Function

The balance between ATR and DDK activities controls TopBP1-mediated locking of dormant origins at the pre-IC stage

Mapping Replication Timing in Single Mammalian Cells

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