ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases.
A new member of the human origin recognition complex (ORC) was cloned and identified as ORC5L. HsORC5p is a 50-kDa protein whose sequence is 38% identical and 62% similar to ORC5p from Drosophila melanogaster. Two alleles of ORC5L were identified, one with and one without an evolutionarily conserved purine nucleotide binding motif. HsORC5p is precipitated from cell extracts with HsORC2p and HsORC4p, indicating that it is part of the putative human ORC. The bulk of HsORC5p is in an insoluble nuclear fraction, whereas the other known human ORC subunits (HsORC1p, HsORC2p, and HsORC4p) are easily extracted in the nuclear-soluble fractions and in S100 (HsORC1p). In addition, we identified an alternatively spliced mRNA from the same locus (HsORC5T). HsORC5Tp also formed a complex with HsORC4p but not with HsORC2p, suggesting it may play a regulatory role in the assembly of different ORC subcomplexes. 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. Finally, the gene for ORC5L is located at chromosome 7, band q22, in the minimal region deleted in 10% of uterine leiomyomas and in 10-20% of acute myeloid leukemias and myelodysplastic syndromes.
Division of Molecular Oncology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
D G
DG
Quintana
K C
KC
Thome
Z H
ZH
Hou
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AH
Ligon
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CC
Morton
A
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Dutta
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007889:Leiomyoma / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D051738:Origin Recognition Complex; D018741:Replication Origin; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000737:chemistry; D014018:Tissue Distribution; D014594:Uterine Neoplasms / Q000235:genetics*
D004268:DNA-Binding Proteins; C497226:ORC5 protein, human; D051738:Origin Recognition Complex