A group of homologous DNA replication origins and replicators dispersed throughout the human genome & anticancer compounds targeting DNA replication initiation proteins from Chinese medicinal herbals

2010 ◽  
Author(s):  
Ziyi Wang
Keyword(s):  
Dna Replication ◽  
Human Genome ◽  
Replication Initiation ◽  
Replication Origins ◽  
Anticancer Compounds ◽  
Dna Replication Initiation ◽  
Dna Replication Origins ◽  
Replication Initiation Proteins

scholarly journals A predictable conserved DNA base composition signature defines human core DNA replication origins

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ildem Akerman ◽  
Bahar Kasaai ◽  
Alina Bazarova ◽  
Pau Biak Sang ◽  
Isabelle Peiffer ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Sequence ◽  
Cell Types ◽  
Replication Initiation ◽  
Replication Origins ◽  
Dna Base Composition ◽  
Dna Replication Initiation ◽  
Sequence Elements ◽  
Dna Replication Origins ◽  
Genomic Regions

Abstract DNA replication initiates from multiple genomic locations called replication origins. In metazoa, DNA sequence elements involved in origin specification remain elusive. Here, we examine pluripotent, primary, differentiating, and immortalized human cells, and demonstrate that a class of origins, termed core origins, is shared by different cell types and host ~80% of all DNA replication initiation events in any cell population. We detect a shared G-rich DNA sequence signature that coincides with most core origins in both human and mouse genomes. Transcription and G-rich elements can independently associate with replication origin activity. Computational algorithms show that core origins can be predicted, based solely on DNA sequence patterns but not on consensus motifs. Our results demonstrate that, despite an attributed stochasticity, core origins are chosen from a limited pool of genomic regions. Immortalization through oncogenic gene expression, but not normal cellular differentiation, results in increased stochastic firing from heterochromatin and decreased origin density at TAD borders.

scholarly journals Archaeal Orc1 protein interacts with T-rich single-stranded DNA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Katarzyna Wegrzyn ◽  
Igor Konieczny
Keyword(s):  
Dna Replication ◽  
Replication Initiation ◽  
Single Stranded Dna ◽  
Dna Replication Initiation ◽  
Double Stranded Dna ◽  
Nucleoprotein Complexes ◽  
Eukaryotic Organisms ◽  
Replication Initiation Proteins ◽  
Hydrolysis Of ◽  
Replication Activity

Abstract Objective The ability to form nucleoprotein complexes is a fundamental activity of DNA replication initiation proteins. They bind within or nearby the region of replication origin what results in melting of a double-stranded DNA (dsDNA) and formation of single-stranded DNA (ssDNA) region where the replication machinery can assemble. For prokaryotic initiators it was shown that they interact with the formed ssDNA and that this interaction is required for the replication activity. The ability to interact with ssDNA was also shown for Saccharomyces cerevisiae replication initiation protein complex ORC. For Archaea, which combine features of both prokaryotic and eukaryotic organisms, there was no evidence whether DNA replication initiators can interact with ssDNA. We address this issue in this study. Results Using purified Orc1 protein from Aeropyrum pernix (ApOrc1) we analyzed its ability to interact with ssDNA containing sequence of an AT-rich region of the A. pernix origin Ori1 as well as with homopolymers of thymidine (polyT) and adenosine (polyA). The Bio-layer interferometry, surface plasmon resonance and microscale thermophoresis showed that the ApOrc1 can interact with ssDNA and it binds preferentially to T-rich ssDNA. The hydrolysis of ATP is not required for this interaction.

scholarly journals The interaction networks of the budding yeast and human DNA replication-initiation proteins

Cell Cycle ◽  
2019 ◽  
Vol 18 (6-7) ◽  
pp. 723-741 ◽  
Author(s):  
Rentian Wu ◽  
Aftab Amin ◽  
Ziyi Wang ◽  
Yining Huang ◽  
Marco Man-Hei Cheung ◽  
...  
Keyword(s):  
Dna Replication ◽  
Budding Yeast ◽  
Replication Initiation ◽  
Interaction Networks ◽  
Dna Replication Initiation ◽  
Human Dna ◽  
Replication Initiation Proteins

scholarly journals Specification of Regions of DNA Replication Initiation during Embryogenesis in the 65-KilobaseDNApolα-dE2F Locus of Drosophila melanogaster

1999 ◽  
Vol 19 (1) ◽  
pp. 547-555 ◽  
Author(s):  
Takayo Sasaki ◽  
Tomoyuki Sawado ◽  
Masamitsu Yamaguchi ◽  
Tomoyuki Shinomiya
Keyword(s):  
Dna Replication ◽  
Cultured Cells ◽  
Early Stage ◽  
Replication Initiation ◽  
Replication Origins ◽  
Coding Region ◽  
Promoter Regions ◽  
Dna Replication Initiation ◽  
Differentiated Cells ◽  
Active Promoter

ABSTRACT In the early stage of Drosophila embryogenesis, DNA replication initiates at unspecified sites in the chromosome. In contrast, DNA replication initiates in specified regions in cultured cells. We investigated when and where the initiation regions are specified during embryogenesis and compared them with those observed in cultured cells by two-dimensional gel methods. In the DNA polymerase α gene (DNApolα) locus, where an initiation region,oriDα, had been identified in cultured Kc cells, repression of origin activity in the coding region was detected after formation of cellular blastoderms, and the range of the initiation region had become confined by 5 h after fertilization. During this work we identified other initiation regions between oriDα and the Drosophila E2F gene (dE2F) downstream of DNApolα. At least four initiation regions showing replication bubbles were identified in the 65-kbDNApolα-dE2F locus in 5-h embryos, but only two were observed in Kc cells. These results suggest that the specification levels of origin usage in 5-h embryos are in the intermediate state compared to those in more differentiated cells. Further, we found a spatial correlation between the active promoter regions fordE2F and the active initiation zones of replication. In 5-h embryos, two known transcripts differing in their first exons were expressed, and two regions close to the respective promoter regions for both transcripts functioned as replication origins. In Kc cells, only one transcript was expressed and functional replication origins were observed only in the region including the promoter region for this transcript.

scholarly journals DNA Replication Origins Fire Stochastically in Fission Yeast

2006 ◽  
Vol 17 (1) ◽  
pp. 308-316 ◽  
Author(s):  
Prasanta K. Patel ◽  
Benoit Arcangioli ◽  
Stephen P. Baker ◽  
Aaron Bensimon ◽  
Nicholas Rhind
Keyword(s):  
Dna Replication ◽  
Fission Yeast ◽  
Replication Initiation ◽  
Epigenetic Mechanism ◽  
Replication Origins ◽  
Origin Firing ◽  
Cell Cycles ◽  
Initiation Of Replication ◽  
Dna Combing ◽  
Dna Replication Origins

DNA replication initiates at discrete origins along eukaryotic chromosomes. However, in most organisms, origin firing is not efficient; a specific origin will fire in some but not all cell cycles. This observation raises the question of how individual origins are selected to fire and whether origin firing is globally coordinated to ensure an even distribution of replication initiation across the genome. We have addressed these questions by determining the location of firing origins on individual fission yeast DNA molecules using DNA combing. We show that the firing of replication origins is stochastic, leading to a random distribution of replication initiation. Furthermore, origin firing is independent between cell cycles; there is no epigenetic mechanism causing an origin that fires in one cell cycle to preferentially fire in the next. Thus, the fission yeast strategy for the initiation of replication is different from models of eukaryotic replication that propose coordinated origin firing.

scholarly journals Investigating the role of Rts1 in DNA replication initiation

2018 ◽  
Vol 3 ◽  
pp. 23 ◽  
Author(s):  
Ana B.A. Wallis ◽  
Conrad A. Nieduszynski
Keyword(s):  
Dna Replication ◽  
Temperature Sensitivity ◽  
Protein Phosphatase ◽  
Dna Helicase ◽  
Replication Initiation ◽  
Replication Origins ◽  
Origin Firing ◽  
Replication Factor ◽  
Dna Replication Initiation ◽  
Genomic Screen

Background: Understanding DNA replication initiation is essential to understand the mis-regulation of replication seen in cancer and other human disorders. DNA replication initiates from DNA replication origins. In eukaryotes, replication is dependent on cell cycle kinases which function during S phase. Dbf4-dependent kinase (DDK) and cyclin-dependent kinase (CDK) act to phosphorylate the DNA helicase (composed of mini chromosome maintenance proteins: Mcm2-7) and firing factors to activate replication origins. It has recently been found that Rif1 can oppose DDK phosphorylation. Rif1 can recruit protein phosphatase 1 (PP1) to dephosphorylate MCM and restricts origin firing. In this study, we investigate a potential role for another phosphatase, protein phosphatase 2A (PP2A), in regulating DNA replication initiation. The PP2A regulatory subunit Rts1 was previously identified in a large-scale genomic screen to have a genetic interaction with ORC2 (a DNA replication licensing factor). Deletion of RTS1 synthetically rescued the temperature-sensitive (ts-) phenotype of ORC2 mutants. Methods: We deleted RTS1 in multiple ts-replication factor Saccharomyces cerevisiae strains, including ORC2.  Dilution series assays were carried out to compare qualitatively the growth of double mutant ∆rts1 ts-replication factor strains relative to the respective single mutant strains.   Results: No synthetic rescue of temperature-sensitivity was observed. Instead we found an additive phenotype, indicating gene products function in separate biological processes. These findings are in agreement with a recent genomic screen which found that RTS1 deletion in several ts-replication factor strains led to increased temperature-sensitivity. Conclusions: We find no evidence that Rts1 is involved in the dephosphorylation of DNA replication initiation factors.

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