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| http://dx.doi.org/10.4161/cc.26132 | DOI Listing |
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The six subunit Origin Recognition Complex (ORC) loads excess MCM2-7 on chromosomes to promote initiation of DNA replication and is believed to be important for origin specification. Mapping of origins in cancer cell lines engineered to delete three of the subunits, , or shows that specific origins are still used and are mostly at the same sites in the genome as in wild type cells. The few hundred origins that were up-regulated in the absence of ORC suggest that GC/TA skewness and simple repeat sequences facilitate, but are not essential for, origin selection in the absence of the six-subunit ORC.
View Article and Find Full Text PDFThe herpes simplex virus alkaline nuclease is required to maintain replication fork progression.
J Virol
December 2024
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Article Synopsis
- - The herpes simplex virus (HSV-1) relies on its UL12 nuclease for effective DNA replication, as a mutant strain lacking UL12 (AN-1) shows normal replication but fails to package its DNA into infectious virus particles.
- - Researchers used a method called iPOND combined with SILAC to analyze protein interactions at DNA replication sites, discovering that AN-1 lacks 60 essential host replication proteins compared to the wild-type virus, KOS.
- - This study highlights how essential UL12 is for proper DNA replication fork function, as its absence leads to stalled replication processes, which could contribute to HSV-1-related complications in immunocompromised individuals.
The six subunit ORC is essential for initiation of DNA replication in eukaryotes. Cancer cell-lines in culture can survive and replicate DNA replication after genetic inactivation of individual ORC subunits, ORC1, ORC2 or ORC5. In primary cells, ORC1 was dispensable in the mouse liver for endo-reduplication, but this could be explained by the ORC1 homolog, CDC6, substituting for ORC1 to restore functional ORC.
View Article and Find Full Text PDFIntegrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap.
Elife
April 2024
Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, United States.
Based on experimentally determined average inter-origin distances of ~100 kb, DNA replication initiates from ~50,000 origins on human chromosomes in each cell cycle. The origins are believed to be specified by binding of factors like the origin recognition complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and five ORC-binding profiles to critically evaluate whether the most reproducible origins are specified by these features.
View Article and Find Full Text PDFBased on experimentally determined average inter-origin distances of ∼100 kb, DNA replication initiates from ∼50,000 origins on human chromosomes in each cell cycle. The origins are believed to be specified by binding of factors like the Origin Recognition Complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and 5 ORC-binding profiles to critically evaluate whether the most reproducible origins are specified by these features.
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