HsOrc4-dependent DNA remodeling of the ori-β DHFR replicator
-
Branko Tomic
and
Jelena Kusic-Tisma
Abstract
Replication of DNA in multicellular organisms initiates from origin of replication (ori) sequences, which significantly differ in length and complexity. One of the best characterized is hamster dihydrofolate reductase (DHFR), which contains the ori-β sequence with several functionally relevant domains, such as an AT-rich region, dinucleotide repeat element (DNR), sequence-induced bend DNA (BEND) and a RIP60 protein-binding site (RIP60). Prior to initiation, ori sequences are recognized by origin recognition complex (ORC), which is a hetero hexamer complex that serves as the landing pad for proteins of the pre-replication complex. The function of each ORC subunit is still unclear. In this study, we analyze the function of subunit 4 of the human ORC complex (HsOrc4) in interaction with a plasmid bearing the ori-β DHFR sequence. We show that the topologically closed DHFR ori-β replicator contains a bubble-like structure within its AT-rich region and that it is reversibly modified in the interaction with HsOrc4. The non-canonical structure of the AT-rich region in the topologically closed ori sequence is recognized and changed by HsOrc4 using the energy of supercoiled DNA. These findings could help to further elucidate DNA replication and its possible association with human genetic diseases.
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© 2015
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Articles in the same Issue
- Elevated pressure enhanced TRAIL-induced apoptosis in hepatocellular carcinoma cells via ERK1/2-inactivation
- HsOrc4-dependent DNA remodeling of the ori-β DHFR replicator
- Is Iron Chelation Important in Preventing Glycation of Bovine Serum Albumin in Vitro?
- The transition of the 37-kDa laminin receptor (RPSA) to higher molecular weight species: SUMOylation or artifact?
- Mechanical strain affects some microRNA profiles in pre-oeteoblasts.
- Sphingosine-1-phosphate induces the migration and angiogenesis of EPCs through the Akt signaling pathway via sphingosine-1-phosphate receptor 3/platelet-derived growth factor receptor-β
- Bioinformatics-based molecular classification of Arthrobacter plasmids
- Ras Transformation Overrides a Proliferation Defect Induced by Tpm3.1 Knockout
- The advanced lipoxidation end product precursor malondialdehyde induces IL-17E expression and skews lymphocytes to the Th17 subset
- On Application of Langevin Dynamics in Logarithmic Potential to Model Ion Channel Gate Activity
- Superoxide Dismutase 2 Polymorphisms and Osteoporosis in Asian Indians: A Genetic Association Analysis
