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 evol utionarily conserved purine nucleotide binding motif, HsORC5p is preci pitated from cell extracts with HsORC2p and HsORC4p, indicating that i t is part of the putative human ORC, The bulk of HsORC5p is in an inso luble nuclear fraction, whereas the other known human ORC subunits (Hs ORC1p, HsORC2p, and HsORC4p) are easily extracted in the nuclear-solub le fractions and in S100 (HsORC1p). In addition, we identified an alte rnatively spliced mRNA from the same locus (HsORC5T), HsORC5Tp also fo rmed a complex with HsORC4p but not with HsORC2p, suggesting it may pl ay a regulatory role in the assembly of different ORC subcomplexes, Hs ORC5, HsORC5T, and HsORC4 transcripts are abundant in spleen, ovary, a nd prostate in addition to tissues with high levels of DNA replication like testes and colon mucosa, implicating the human ORC proteins in f unctions besides DNA replication. Finally, the gene for ORC5L is locat ed at chromosome 7, band q22, in the minimal region deleted in 10% of uterine leiomyomas and in 10-20% of acute myeloid leukemias and myelod ysplastic syndromes.