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In order to study the effects of Meier-Gorlin syndrome (MGS (show GYS1 Proteins)) mutation in an animal model system, MGS (show GYS1 Proteins) mutation in Orc6 was introduced and established Drosophila model of MGS (show GYS1 Proteins).
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 (show SEPT1 Proteins) complex is dependent on the coiled-coil domain of Pnut, and suggest an active role for Orc6 in septin (show SEPT1 Proteins) 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 (show GYS1 Proteins)) 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 (show ORC1L Proteins)-Orc5 (show ORC5 Proteins) but also with the initiation factor Cdc6 (show CDC6 Proteins), 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 (show GTF2B Proteins).
results implicate Orc6 as an essential gene that coordinates chromosome replication and segregation with cytokinesis
Study using HCT116 haplo-insufficient (show TGFb Proteins) cells and Orc2 hypomorphic cells demonstrates that the binding of human Ku to replication origins precedes that of Orc-3 (show ORC3 Proteins), -4, and -6 subunit binding.
Orc6 has a role in sensitizing human colon cancer cells to 5-fluorouracil and cisplatin
Study reports that ORC6L is another component required for acquisition of DNA replication competence that is absent in mouse oocytes.
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