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Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C).
HsOrc4 could have a fundamental function in the process of initiation of replication by remodeling the structure of origin of replication using the energy of supercoiled DNA.
compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4
identified three different mutations in the gene encoding ORC4, a component of the eukaryotic origin recognition complex, in five individuals with Meier-Gorlin syndrome
DNA binding activity of HsOrc4 depends on length and structure of DNA with triplex being the protein's preferred binding target.
Study using HCT116 haplo-insufficient cells and Orc2 hypomorphic cells demonstrates that the binding of human Ku to replication origins precedes that of Orc-3, -4, and -6 subunit binding.
describe 3 patients with B-cell lymphoproliferative disorders (2 with non-Hodgkin lymphoma and 1 with nonsecretory multiple myeloma) carrying a novel A286V mutation within ORC4L gene
Biochemical characterization of the mouse homolog
Together, these data demonstrate that ORC4 oligomerization is required to form the ORC4 cage and that it is required for polar body extrusion.
ORC4 surrounds the chromatin that will be extruded in the polar body in both female meiotic divisions, then makes a transition from the cytoplasm to the chromosomes at zygotic anaphase, suggesting multiple roles for this replication licensing protein.
The interaction of the Drosophila ENY2 protein with the ORC complex subunits was investigated. It is found that ORC4 and ORC6 subunits directly interact with ENY2.
Spotted-dick is a zinc-finger protein of Drosophila required for expression of Orc4 and S phase
The origin recognition complex (ORC) is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene.
origin recognition complex subunit 4
, origin recognition complex, subunit 4 homolog
, origin recognition complex, subunit 4-like