scholarly journals Nucleosomes influence multiple steps during replication initiation

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ishara F Azmi ◽  
Shinya Watanabe ◽  
Michael F Maloney ◽  
Sukhyun Kang ◽  
Jason A Belsky ◽  
...  
Keyword(s):  
Dna Replication ◽  
Chromatin Remodeling ◽  
Replication Origin ◽  
Replication Initiation ◽  
Dna Templates ◽  
Helicase Loading ◽  
Origin Activation ◽  
Nucleosomal Dna ◽  
Origin Licensing ◽  
The Impact

Eukaryotic replication origin licensing, activation and timing are influenced by chromatin but a mechanistic understanding is lacking. Using reconstituted nucleosomal DNA replication assays, we assessed the impact of nucleosomes on replication initiation. To generate distinct nucleosomal landscapes, different chromatin-remodeling enzymes (CREs) were used to remodel nucleosomes on origin-DNA templates. Nucleosomal organization influenced two steps of replication initiation: origin licensing and helicase activation. Origin licensing assays showed that local nucleosome positioning enhanced origin specificity and modulated helicase loading by influencing ORC DNA binding. Interestingly, SWI/SNF- and RSC-remodeled nucleosomes were permissive for origin licensing but showed reduced helicase activation. Specific CREs rescued replication of these templates if added prior to helicase activation, indicating a permissive chromatin state must be established during origin licensing to allow efficient origin activation. Our studies show nucleosomes directly modulate origin licensing and activation through distinct mechanisms and provide insights into the regulation of replication initiation by chromatin.

The programme of DNA replication: beyond genome duplication

2013 ◽  
Vol 41 (6) ◽  
pp. 1720-1725 ◽  
Author(s):  
Blanca Gómez-Escoda ◽  
Pei-Yun Jenny Wu
Keyword(s):  
Dna Replication ◽  
Cell Growth ◽  
Dna Synthesis ◽  
Genetic Information ◽  
Replication Origin ◽  
Genome Duplication ◽  
Replication Initiation ◽  
Origin Activation ◽  
Key Steps ◽  
Cell Growth And Proliferation

The accurate duplication and transmission of genetic information is critical for cell growth and proliferation, and this is ensured in part by the multi-layered regulation of DNA synthesis. One of the key steps in this process is the selection and activation of the sites of replication initiation, or origins, across the genome. Interestingly, origin usage changes during development and in different pathologies, suggesting an integral interplay between the establishment of replication initiation along the chromosomes and cellular function. The present review discusses how the spatiotemporal organization of replication origin activation may play crucial roles in the control of biological events.

scholarly journals Transcription drives DNA replication initiation and termination in human cells

2018 ◽  
Author(s):  
Yu-Hung Chen ◽  
Sarah Keegan ◽  
Malik Kahli ◽  
Peter Tonzi ◽  
David Fenyö ◽  
...  
Keyword(s):  
Dna Replication ◽  
Rna Polymerase Ii ◽  
Replication Fork ◽  
Human Cells ◽  
Replication Initiation ◽  
Origin Firing ◽  
Dna Replication Initiation ◽  
Origin Activation ◽  
Dna Replication Origins ◽  
The Impact

ABSTRACTThe locations of active DNA replication origins in the human genome, and the determinants of origin activation, remain controversial. Additionally, neither the predominant sites of replication termination nor the impact of transcription on replication-fork mobility have been defined. We demonstrate that replication initiation occurs preferentially in the immediate vicinity of the transcription start site of genes occupied by high levels of RNA polymerase II, ensuring co-directional replication of the most highly transcribed genes. Further, we demonstrate that dormant replication origin firing represents the global activation of pre-existing origins. We also show that DNA replication naturally terminates at the polyadenylation site of transcribed genes. During replication stress, termination is redistributed to gene bodies, generating a global reorientation of replication relative to transcription. Our analysis provides a unified model for the coupling of transcription with replication initiation and termination in human cells.

scholarly journals Human RIF 1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress origin activation

EMBO Reports ◽  
2017 ◽  
Vol 18 (3) ◽  
pp. 403-419 ◽  
Author(s):  
Shin‐ichiro Hiraga ◽  
Tony Ly ◽  
Javier Garzón ◽  
Zuzana Hořejší ◽  
Yoshi‐nobu Ohkubo ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Phosphatase ◽  
Replication Origin ◽  
Protein Phosphatase 1 ◽  
Origin Activation ◽  
Origin Licensing ◽  
Dna Replication Origin

scholarly journals High-throughput analysis of DNA replication in single human cells reveals constrained variability in the location and timing of replication initiation

2021 ◽  
Author(s):  
Dashiell J Massey ◽  
Amnon Koren
Keyword(s):  
Dna Replication ◽  
Replication Origin ◽  
Replication Timing ◽  
S Phase ◽  
Human Cells ◽  
Replication Initiation ◽  
High Throughput Analysis ◽  
Timing Variability ◽  
Fixed Set ◽  
Fixed Order

DNA replication occurs throughout the S phase of the cell cycle, initiating from replication origin loci that fire at different times. Debate remains about whether origins are a fixed set of loci used across all cells or a loose agglomeration of potential origins used stochastically in individual cells, and about how consistent their firing time during S phase is across cells. Here, we develop an approach for profiling DNA replication in single human cells and apply it to 2,305 replicating cells spanning the entire S phase. The resolution and scale of the data enabled us to specifically analyze initiation sites and show that these sites have confined locations that are consistently used among individual cells. Further, we find that initiation sites are activated in a similar, albeit not fixed, order across cells. Taken together, our results suggest that replication timing variability is constrained both spatially and temporally, and that the degree of variation is consistent across human cell lines.

scholarly journals Concerted Loading of Mcm2–7 Double Hexamers around DNA during DNA Replication Origin Licensing

Cell ◽  
2009 ◽  
Vol 139 (4) ◽  
pp. 719-730 ◽  
Author(s):  
Dirk Remus ◽  
Fabienne Beuron ◽  
Gökhan Tolun ◽  
Jack D. Griffith ◽  
Edward P. Morris ◽  
...  
Keyword(s):  
Dna Replication ◽  
Replication Origin ◽  
Origin Licensing ◽  
Dna Replication Origin
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