High impact information on Orc2

• The origin recognition complex (ORC) is required to initiate eukaryotic DNA replication and also engages in transcriptional silencing in S. cerevisiae [1].
• We observed a striking preferential but not exclusive association of Drosophila ORC2 with heterochromatin on interphase and mitotic chromosomes [1].
• HP1, a heterochromatin-localized protein required for position effect variegation (PEV), colocalized with DmORC2 at these sites [1].
• Interestingly, a dE2F mutant predicted to lack the carboxy-terminal transcriptional activation and RB-binding domain does not abolish ORC2 localization and shows premature chorion amplification [2].
• We isolated mutations in Drosophila E2F and DP that affect chorion gene amplification and ORC2 localization in the follicle cells [2].

Biological context of Orc2

• Taken together, the data suggest a model in which ACE3 and ori-beta nucleate the formation of a ORC2-containing chromatin structure that spreads along the chromosome in a mechanism dependent upon chiffon [3].
• The origin recognition complex (ORC) is a six subunit complex required for eukaryotic DNA replication initiation and for silencing of the heterochromatic mating type loci in Saccharomyces cerevisiae [4].
• The location of origins of DNA replication within the Saccharomyces cerevisiae genome is primarily determined by the origin recognition complex (ORC) interacting with specific DNA sequences [5].
• We report here that the smallest Drosophila ORC subunit, Orc6, is a DNA binding protein that is necessary for the DNA binding and DNA replication functions of ORC [6].
• One of the suppressor genes identified was the Drosophila orc2 gene [7].

Anatomical context of Orc2

• Antibody to the origin recognition complex subunit 2 (ORC2) recognizes large foci that localize to the endogenous chorion gene loci and to active transgenic constructs at the beginning of amplification [3].
• In the follicle cells of the ovary, the ORC2 protein is localized throughout the follicle cell nuclei when they are undergoing polyploid genomic replication, and its levels appear constant in both S and G phases [2].
• HsORC5, HsORC5T, and HsORC4 transcripts are abundant in spleen, ovary, and prostate in addition to tissues with high levels of DNA replication like testes and colon mucosa, implicating the human ORC proteins in functions besides DNA replication [8].
• ORC activity is not restored until mitosis is complete and a nuclear membrane is present [9].
• A female-sterile allele of k43 specifically reduces chorion gene amplification in ovarian follicle cells. k43 was cloned by chromosomal walking, and the identification of the k43 gene was confirmed by phenotypic rescue and sequence analysis of mutant alleles [10].

Associations of Orc2 with chemical compounds

• The origin recognition complex (ORC), first identified in Saccharomyces cerevisiae (sc), is a six-subunit protein complex that binds to DNA origins [11].

Regulatory relationships of Orc2

• The results, taken together, demonstrate that the orc2 gene is under the control of DREF pathway [7].

Other interactions of Orc2

• Mutation of the histone deacetylase (HDAC) Rpd3 induced genome-wide hyperacetylation, genomic replication and a redistribution of the origin-binding protein ORC2 in amplification-stage cells, independent of effects on transcription [12].
• Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway [7].
• One long intergenic sequence, located in the distal 5' flanking region of gene s18, is homologous to ACE3, a major amplification control element and contains an 80-bp A/T-rich sequence, known to stimulate strong binding of the origin recognition complex (ORC) in D. melanogaster [13].

Analytical, diagnostic and therapeutic context of Orc2

• Studies reported here provide the first functional dissection of a metazoan initiator and highlight the basic conserved and divergent features among Drosophila and budding yeast ORC complexes [14].
• Lethal alleles of the Drosophila k43 gene result in small or missing imaginal discs, greatly reduced mitotic index, and fragmented and abnormally condensed chromosomes [10].

References