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J Biol Chem, Vol. 273, Issue 29, 18205-18209, July 17, 1998
From the Department of Pathology, Brigham and Women's Hospital,
Harvard Medical School, Boston, Massachusetts 02115
In budding yeast Saccharomyces
cerevisiae CDC45 is an essential gene required for
initiation of DNA replication. A structurally related protein Tsd2 is
necessary for DNA replication in Ustilago maydis. We have
identified and cloned the gene for a human protein homologous to the
fungal proteins. The human gene CDC45L is 30 kilobases long
and contains 15 introns. The 16 exons encode a protein of 566 amino
acids. The human protein is 52 and 49.5% similar to CDC45p and Tsd2p,
respectively. The level of CDC45L mRNA peaks at G1-S
transition, but total protein amount remains constant throughout the
cell cycle. Consistent with a role of CDC45L protein in the initiation
of DNA replication it co-immunoprecipitates from cell extracts with a
putative replication initiator protein, human ORC2L. In addition,
subcellular fractionation indicates that the association of the protein
with the nuclear fraction becomes labile as S phase progresses. The
CDC45L gene is located to chromosome 22q11.2 region by
cytogenetics and by fluorescence in situ hybridization.
This region, known as DiGeorge syndrome critical region, is a minimal
area of 2 megabases, which is consistently deleted in DiGeorge syndrome
and related disorders. The syndrome is marked by parathyroid
hypoplasia, thymic aplasia, or hypoplasia and congenital cardiac
abnormalities. CDC45L is the first gene mapped to the
DiGeorge syndrome critical region interval whose loss may negatively
affect cell proliferation.
The Human Homolog of Saccharomyces cerevisiae
CDC45
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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