Poly(ADP-ribose) polymerase (PARP) is an abundant, chromatin-associated, NAD-dependent enzyme that functions in multiple chromosomal processes, including DNA replication and chromatin remodeling. The Epstein-Barr virus (EBV) origin of plasmid replication (OriP) is a dynamic genetic element that confers stable episome maintenance, DNA replication initiation, and chromatin organization functions. OriP function depends on the EBV-encoded origin binding protein EBNA1. We have previously shown that EBNA1 is subject to negative regulation by poly(ADP-ribosyl)ation (PARylation). We now show that PARP1 physically associates with OriP in latently EBV-infected B cells. Short hairpin RNA depletion of PARP1 enhances OriP replication activity and increases EBNA1, origin recognition complex 2 (ORC2), and minichromosome maintenance complex (MCM) association with OriP. Pharmacological inhibitors of PARP1 enhance OriP plasmid maintenance and increase EBNA1, ORC2, and MCM3 occupancy at OriP. PARylation in vitro inhibits ORC2 recruitment and remodels telomere repeat factor (TRF) binding at the dyad symmetry (DS) element of OriP. Purified PARP1 can ribosylate EBNA1 at multiple sites throughout its amino terminus but not in the carboxy-terminal DNA binding domain. We also show that EBNA1 linking regions (LR1 and LR2) can bind directly to oligomers of PAR. We propose that PARP1-dependent PARylation of EBNA1 and adjacently bound TRF2 induces structural changes at the DS element that reduce EBNA1 DNA binding affinity and functional recruitment of ORC.
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http://dx.doi.org/10.1128/JVI.02333-09 | DOI Listing |
Ecol Lett
January 2025
Department of Cellular and Molecular Biology, Harvard University, Cambridge, Massachusetts, USA.
Nucleic Acids Res
December 2024
Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA, 19081USA.
Left-handed G-quadruplexes (LHG4s) belong to a class of recently discovered noncanonical DNA structures under the larger umbrella of G-quadruplex DNAs (G4s). The biological relevance of these structures and their ability to be targeted with classical G4 ligands is underexplored. Here, we explore whether the putative LHG4 DNA sequence from the SLC2A1 oncogene promoter maintains its left-handed characteristics upon addition of nucleotides in the 5'- and 3'-direction from its genomic context.
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Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint.
View Article and Find Full Text PDFVet Sci
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California National Primate Research Center, University of California, Davis, CA 95616, USA.
At the California National Primate Research Center (CNPRC), the preferred housing for rhesus macaques involves maintaining them in complex social groups outdoors, primarily for breeding purposes. This functionally appropriate environment promotes effective coping through the expression of species-typical behaviors and important aspects of species-typical social structure, thus enabling normal animal development, higher reproductive success, and the production of high-quality biological models. Despite the benefits, social housing introduces challenges like trauma from aggressive interactions.
View Article and Find Full Text PDFBiology (Basel)
October 2024
Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
Owing to the taxonomic incongruence between the morphological features and genetic relationships of the group of macaques (genus ), the taxonomy of this macaque group has remained inconclusive. We aimed to resolve the taxonomic quandary and improve our understanding of the historical biogeography of the group by including macaque DNA samples from previously unsampled areas in the Himalayas. We sequenced and analyzed three mitochondrial DNA loci [cytochrome b (CYTB), cytochrome oxidase subunit 1 (COI) and D-loop; 2898 bp] for sequence polymorphism, phylogenetics, species delimitation, and ancestral area reconstruction.
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