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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.
In order to study the effects of Meier-Gorlin syndrome (MGS) mutation in an animal model system, MGS mutation in Orc6 was introduced and established Drosophila model of MGS.
Drosophila Orc6 protein, the smallest subunit of the origin recognition complex (ORC), directly binds to septin complex and facilitates septin filament formation.
Drosophila ORC6 protein cytokinetic function resides in a domain distinct from its replication activity
These studies provide a molecular analysis for the functional requirement of Orc6 in replicative functions of ORC in Drosophila and suggest that Orc6 may contribute to the sequence preferences of ORC in targeting to the origins.
These results show that the interaction of Orc6 with the septin complex is dependent on the coiled-coil domain of Pnut, and suggest an active role for Orc6 in septin complex function.
In a cross-species complementation experiment, the expression of human Orc6 in Drosophila Orc6 mutant cells rescued DNA replication, suggesting that this function of the protein is conserved among metazoans.
The 11-year-old boy with Meier-Gorlin syndrome (MGS) has a homozygous mutation in origin recognition complex, subunit 6 (ORC6) gene mapped to chromosome 16, and his father with heterozygote carrier of ORC6 gene.
The present report expands the clinical phenotype associated with ORC6 mutations to include severely abnormal embryological development suggesting a possible genotype-phenotype correlation.
our results suggest that Meier-Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions
findings show that Orc6 not only interacts with Orc1-Orc5 but also with the initiation factor Cdc6, and that Orc6 functions at different stages of the replication initiation process.
Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB.
results implicate Orc6 as an essential gene that coordinates chromosome replication and segregation with cytokinesis
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.
Orc6 has a role in sensitizing human colon cancer cells to 5-fluorouracil and cisplatin
Functional studies of the Drosophila homolog
Functional studies of the yeast homolog
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. The protein encoded by this gene is a subunit of the ORC complex. Gene silencing studies with small interfering RNA demonstrated that this protein plays an essential role in coordinating chromosome replication and segregation with cytokinesis.
origin recognition complex subunit 6
, origin recognition complex, subunit 6-like
, origin recognition complex, subunit 6 like