Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CDC45 is required for the initiation of DNA replication in Saccharomyces cerevisiae and functions as a DNA polymerase alpha loading factor in Xenopus, but its role in mammalian DNA replication is unknown. To investigate the genetic and physiological functions of CDC45, we used a gene targeting strategy to generate mice lacking a functional CDC45 gene. Homozygous mutant mice lacking a functional CDC45 gene underwent uterine implantation and induced uterine decidualization but did not develop substantially thereafter. Detailed analysis of CDC45 null embryos cultured in vitro revealed impaired proliferation of the inner cell mass. These findings make CDC45 the only putative replication factor experimentally proven to be essential for mammalian development. The CDC45 gene localizes to human chromosome 22q11.2 in the DiGeorge syndrome critical region (DGCR). Almost 90% of individuals with congenital cardiac and craniofacial defects have a monoallelic deletion in the DGCR that includes CDC45. We report here that heterozygous mutant mice develop into adulthood without any apparent abnormalities, so that it is unlikely that hemizygosity of CDC45 alone is responsible for the cardiac and craniofacial defects in the congenital syndromes.
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PMID:Requirement of CDC45 for postimplantation mouse development. 1141 37

We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
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PMID:A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications. 1244 6