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

Many cell division cycle (cdc) mutants of Saccharomyces cerevisiae exhibit elevated mitotic loss of pDK243, a 14-kilobase minichromosome with a centromere and one autonomous replicating sequence (ARS). Tandem copies of different ARSs were added to pDK243. The addition of these ARS clusters to pDK243 had no effect on its mitotic loss in cdc7 (protein kinase), cdc9 (DNA ligase), or cdc16 or cdc17 (DNA polymerase) mutants. However, in cdc6 and cdc14 mutants, the mitotic loss of pDK243 with an ARS cluster was suppressed by a factor of 6-8 compared to pDK243 without the cluster. This suppression was dependent upon the number of ARSs in the cluster and the integrity of the ARS consensus sequence in each ARS of the cluster. ARSs are known to be DNA replication origins. Therefore, the suppression of mini-chromosome loss by ARSs in cdc6 and cdc14 mutants suggests that these mutants are defective in the initiation of DNA replication. Since the CDC6 protein appears to act at the G1/S phase transition, the CDC6 protein may be a factor required at the beginning of S phase to initiate DNA replication at origins. In contrast, the CDC14 protein acts after mitosis. We suggest that the CDC14 protein performs a function late in the cell cycle that may be required for efficient initiation of DNA replication during S phase of the next cell cycle.
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PMID:Addition of extra origins of replication to a minichromosome suppresses its mitotic loss in cdc6 and cdc14 mutants of Saccharomyces cerevisiae. 155 17

We have isolated two high copy, allele-specific suppressors of the temperature sensitivity of mutations in POL1, the gene that encodes the catalytic subunit of DNA polymerase alpha in the yeast Saccharomyces cerevisiae. Both genes, PSP1 and PSP2, also partially suppressed a mutation in POL3 which encodes DNA polymerase delta, and both also affected a mutation in CDC6, which acts in initiation of DNA replication. Suppression was not general, since ts mutations in several genes unrelated to replication were not affected, PSP1 was partially effective on low-copy-number vectors, while PSP2 required high copy numbers. The presence of suppressing plasmids did not alter the steady-state level of Pol1 protein, so suppression does not appear to be due to an increase in production or stability of Pol1p. Deletion of either PSP gene or both in combination resulted in apparently normal viable cells. While neither gene is homologous to genes with known functions, PSP1 and PSP2 both have unusual amino acid compositions: PSP1 is rich in asparagine and glutamine, while PSP2 is rich in asparagine and contains "RGG" motifs that have been associated with RNA-binding proteins. We also describe a transposon-mediated strategy that should be generally effective for rapid characterization of multicopy suppressors.
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PMID:Suppressors of the temperature sensitivity of DNA polymerase alpha mutations in Saccharomyces cerevisiae. 952 27

Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations.
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PMID:Structure of the active form of human origin recognition complex and its ATPase motor module. 2811 45