The human homolog of Saccharomyces cerevisiae CDC45.
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.
Saha
P
P
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Thome
K C
KC
Yamaguchi
R
R
Hou
Z
Z
Weremowicz
S
S
Dutta
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D002455:Cell Division; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D004062:DiGeorge Syndrome / Q000235:genetics*; D005656:Fungal Proteins; D016193:G1 Phase; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment
C102209:CDC45 protein, S cerevisiae; C113571:CDC45 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C104386:TSD2 protein, Ustilago maydis