Common structural features of replication origins in all life forms

Boulikas, Teni

doi:10.1002/(sici)1097-4644(19960301)60:3<297::aid-jcb2>3.0.co;2-r

Cited by 58 publications

(28 citation statements)

References 155 publications

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“…This region, which was deleted from both the ⌬NE and the ⌬NS constructs, was designated Rep-I-1. Interestingly, the Rep-I-1 region contains a putative ORC binding site (8) and a putative cell cycledependent DNase-hypersensitive region (9,10,18,19).…”

Section: Vol 24 2004 the ␤-Globin Ir Contains Two Replicators 3375mentioning

confidence: 99%

“…Replication initiation sites, including the ␤-globin replicator, share some common features (22), but unlike genomic replicators in budding yeast, they do not exhibit a clear consensus sequence. These initiation sites tend to contain AT-rich regions, asymmetric purine:pyrimidine stretches, matrix/scaffolding attachment regions, potential cruciform structures, and regions that resemble yeast origin recognition complex (ORC) binding sites (8,9,44). Such sequence features are present within the ␤-globin IR; however, similar regions are also found in sequence elements that do not initiate DNA replication.…”

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confidence: 99%

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The Human β-Globin Replication Initiation Region Consists of Two Modular Independent Replicators

Wang

Lin

Brooks

et al. 2004

Molecular and Cellular Biology

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Previous studies have shown that mammalian cells contain replicator sequences, which can determine where DNA replication initiates. However, the specific sequences that confer replicator activity were not identified. Here we report a detailed analysis of replicator sequences that dictate initiation of DNA replication from the human ␤-globin locus. This analysis suggests that the ␤-globin replication initiation region contains two adjacent, redundant replicators. Each replicator was capable of initiating DNA replication independently at ectopic sites. Within each of these two replicators, we identified short, discrete, nonredundant sequences, which cooperatively determine replicator activity. Experiments with somatic cell hybrids further demonstrated that the requirements for initiation at ectopic sites were similar to the requirements for initiation within native human chromosomes. The replicator clustering and redundancy exemplified in the human ␤-globin locus may account for the extreme difficulty in identifying replicator sequences in mammalian cells and suggest that mammalian replication initiation sites may be determined by cooperative sequence modules.The initiation of DNA replication is a critical step in cell division. However, little is known about the cellular events that transmit signals from the cell cycle machinery to the DNA sequences at which DNA replication initiates. The replicon model of Jacob, Brenner, and Cuzin (28) proposed that all cells regulate DNA replication through the interaction of cis-acting DNA sequences called replicators with trans-acting initiation factors called initiators. Replicators are defined genetically as DNA sequences that contain information that allows them to confer initiation of DNA replication. Replication origins, or replication initiation sites, are determined biochemically and mark the regions from which replication forks emanate. Replicators often colocalize with chromosomal initiation sites in bacteria and in yeast (14). In mammalian cells, DNA sequences meeting the biochemical criteria of replication origins typically do not replicate extrachromosomally, unless they are linked to viral replicons or nuclear retention signals (14). Various biochemical strategies designed to identify initiation regions (IRs) in mammalian cells have sometimes generated conflicting data (8,14). This led to controversy regarding whether replicators exist in mammals and whether initiation of replication in mammalian cells necessitates specific DNA sequences.Mapping of replication initiation profiles in ␤-globin loci provided important clues regarding the roles of specific DNA sequences in directing initiation. The human ␤-globin locus resides on chromosome 11 and includes five genes that encode the ␤-subunit of hemoglobin. Kitsberg et al. (35) demonstrated that replication at this locus initiated from a single IR located between the two adult ␤-like globin genes. The naturally occurring Lepore deletion, which removed the IR, resulted in passive replication of the locus from an outs...

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Section: Vol 24 2004 the ␤-Globin Ir Contains Two Replicators 3375mentioning

confidence: 99%

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confidence: 99%

The Human β-Globin Replication Initiation Region Consists of Two Modular Independent Replicators

Wang

Lin

Brooks

et al. 2004

Molecular and Cellular Biology

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“…as found in the vicinity of replication origins (2). For the identification of ORC binding sites, chromatin immunoprecipitations were performed with Orc2p-specific antibodies as described above.…”

Section: An Orc Binding Site In the Human Top1 Gene Is Located At An mentioning

confidence: 99%

The Origin Recognition Complex Marks a Replication Origin in the Human TOP1 Gene Promoter

Keller

Ladenburger

Kremer

et al. 2002

Journal of Biological Chemistry

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The locations of the origin recognition complex (ORC) in mammalian genomes have been elusive. We have therefore analyzed the DNA sequences associated with human ORC via in vivo cross-linking and chromatin immunoprecipitation. Antibodies specific for hOrc2 protein precipitate chromatin fragments that also contain other ORC proteins, suggesting that the proteins form multisubunit complexes on chromatin in vivo. A binding region for ORC was identified at the CpG island upstream of the human TOP1 gene. Nascent strand abundance assays show that the ORC binding region coincides with an origin of bidirectional replication. The TOP1 gene includes two well characterized matrix attachment regions. The matrix attachment region elements analyzed contain no ORC and constitute no sites for replication initiation. In initial attempts to use the chromatin immunoprecipitation technique for the identification of additional ORC sites in the human genome, we isolated a sequence close to another actively transcribed gene (TOM1) and an alphoid satellite sequence that underlies centromeric heterochromatin. Nascent strand abundance assays gave no indication that the heterochromatin sequence serves as a replication initiation site, suggesting that an ORC on this site may perform functions other than replication initiation.Origins of DNA replication are the chromosomal regions where DNA replication forks for bidirectional duplication of replicons are established. The large and discontinuous genomes of eukaryotes require a large number of origins that are distributed throughout the genome to guarantee a complete replication within the limited time of the S phase in a cell division cycle (for reviews, see Refs. 1-9. The best characterized eukaryotic origins are those of the budding yeast Saccharomyces cerevisiae because they function as sites of replication initiation in extrachromosomal plasmid DNA and are, therefore, amenable to detailed molecular analyses (10, 11). Prototypic budding yeast origin (autonomously replicating sequences (ARSs) 1 ) are composed of 100 -200 base pairs and contain several essential sequence elements including a domain A with the AT-rich ARS consensus sequence and three short stimulatory elements, B1-B3, which are functionally important but divergent in sequence (12). The ARS consensus sequence and the adjacent B1 domain element constitute a binding site for proteins of the origin recognition complex (ORC), whereas the B3 domain element forms a binding site for the transcription factor Abf1 in some, but not all yeast origins (13).ORC is a multimeric protein complex composed of six essential subunits (Orc1p-Orc6p) that associate in an ATP-dependent manner with ARSs (13-15). The major known function of ORC appears to be the recruitment of factors such as Cdc6, Mcm proteins, and others for the formation of functional prereplication complexes (16 -19).Origins of replication in multicellular organisms can usually not be investigated by ARS assays. Therefore, biochemical procedures such as two-dimensional gel electrop...

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“…Active regulatory sequences either as origin of replication or as promoter-enhancer have been shown to exhibit nucleosomefree conformation and are hypersensitive to nuclease digestion (7,29). The special nucleoprotein organization at the regulatory sequences has also been shown to establish a nucleosome phase in chromatin (52,73,76,92).…”

Section: Resultsmentioning

confidence: 99%

“…Evidence for coupling or a correlation between transcription and replication processes has also been observed in Bacillus subtilis (42), in Physarum (64), in temporal regulation of transcription in active genes in early S phase (26, 37), and in several mammalian genes (5,41,71,94). Transcription factors have also been implicated in regulating replication origins (7,13,18,19,30,31,38,52).To understand the role of transcription factor regulatory elements and the transcription process in the regulation of eukaryotic DNA replication, we studied the effect of strong promoter-enhancer on the simian virus 40 (SV40) replication origin. Our results indicate that the human cytomegalovirus (HCMV) immediate early (IE) gene enhancer inhibits SV40 origin-dependent replication in a position-and dose-dependent manner.…”

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confidence: 99%

Interference of the Simian Virus 40 Origin of Replication by the Cytomegalovirus Immediate Early Gene Enhancer: Evidence for Competition of Active Regulatory Chromatin Conformation in a Single Domain

Chen

Tseng

Chu³

et al. 2000

Molecular and Cellular Biology

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Replication origins are often found closely associated with transcription regulatory elements in both prokaryotic and eukaryotic cells. To examine the relationship between these two elements, we studied the effect of a strong promoter-enhancer on simian virus 40 (SV40) DNA replication. The human cytomegalovirus (CMV) immediate early gene enhancer-promoter was found to exert a strong inhibitory effect on SV40 origin-based plasmid replication in Cos-1 cells in a position-and dose-dependent manner. Deletion analysis indicated that the effect was exerted by sequences located in the enhancer portion of the CMV sequence, thus excluding the mechanism of origin occlusion by transcription. Insertion of extra copies of the SV40 origin only partially alleviated the inhibition. Analysis of nuclease-sensitive cleavage sites of chromatin containing the transfected plasmids indicate that the chromatin was cleaved at one of the regulatory sites in the plasmids containing more than one regulatory site, suggesting that only one nuclease-hypersensitive site existed per chromatin. A positive correlation was found between the degree of inhibition of DNA replication and the decrease of P1 cleavage frequency at the SV40 origin. The CMV enhancer was also found to exhibit an inhibitory effect on the CMV enhancer-promoter driving chloramphenicol acetyltransferase expression in a dose-dependent manner. Together these results suggest that inhibition of SV40 origin-based DNA replication by the CMV enhancer is due to intramolecular competition for the formation of active chromatin structure.A majority of DNA replication origins in both prokaryotic (3,11,35,42,53,56,59) and eukaryotic (1, 5, 12, 17-19, 24, 25, 36, 38, 41, 43, 48, 60, 62-66, 68, 71, 75, 78, 81, 83, 84, 93-95) cells are closely associated with a transcription unit. Recent characterization of origins of replication in mammalian cells has shown that the origins are located very close to a transcription unit or even within a transcription unit (see review in reference 20). The tight association between transcription and replication units has raised the question of whether or not these two processes are coupled (32,36,42,64,91).Mutual influences between replication and transcription processes have been demonstrated. Activation of DNA replication by transcription has been found in both prokaryotic (3,11,35,56,70) and eukaryotic (48, 60) cells. On the other hand, transcription has been found to suppress replication in bacterial plasmid DNA (47, 53) and in yeast (77, 82), tetrahymena (61), and human (33) cells. Conversely, DNA replication can enhance transcription (28,32,64,90,91). Evidence for coupling or a correlation between transcription and replication processes has also been observed in Bacillus subtilis (42), in Physarum (64), in temporal regulation of transcription in active genes in early S phase (26, 37), and in several mammalian genes (5,41,71,94). Transcription factors have also been implicated in regulating replication origins (7,13,18,19,30,31,38,52).To understand the...

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Common structural features of replication origins in all life forms

Cited by 58 publications

References 155 publications

The Human β-Globin Replication Initiation Region Consists of Two Modular Independent Replicators

The Human β-Globin Replication Initiation Region Consists of Two Modular Independent Replicators

The Origin Recognition Complex Marks a Replication Origin in the Human TOP1 Gene Promoter

Interference of the Simian Virus 40 Origin of Replication by the Cytomegalovirus Immediate Early Gene Enhancer: Evidence for Competition of Active Regulatory Chromatin Conformation in a Single Domain

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