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)

Oncoprotein c-myc is expressed in proliferating but not quiescent mammalian cells, and its overexpression or inappropriate expression is associated with malignant transformation. However, in spite of an intense interest, the normal function of this protein has remained elusive. As a step towards the elucidation of the function of c-myc protein, we studied its distribution within several types of cells, including HL 60, K 562, COLO 320, and CHEF/18 cells. In all of the cells studied, c-myc protein was detected in high molecular weight protein fractions, in 350-600 Kd range, in gel-exclusion chromatography and sucrose gradient centrifugation. This distribution of c-myc protein coincided with the distribution of DNA polymerase alpha and several other enzymes necessary for DNA replication. The data suggest that c-myc product may be a component of the replitase complex of enzymes involved in nuclear DNA replication.
 ...
PMID:Association of c-myc protein with enzymes of DNA replication in high molecular weight fractions from mammalian cells. 164 64

Antibodies against human c-myc protein have been reported to inhibit DNA polymerase activity and endogenous DNA synthesis in isolated nuclei, suggesting a role for c-myc in DNA replication. Using the same antibody preparations, we observed equivalent inhibition of simian virus 40 DNA replication and DNA polymerase alpha and delta activities in vitro, as well as inhibition of DNA synthesis in isolated nuclei. However, the c-myc antibodies could be completely separated from the DNA synthesis inhibition activity. c-myc antibodies prepared in other laboratories also did not interfere with initiation of simian virus 40 DNA replication, DNA synthesis at replication forks, or DNA polymerase alpha or delta activity. Therefore, the previously reported inhibition of DNA synthesis by some antibody preparations resulted from the presence of an unidentified inhibitor of DNA polymerases alpha and delta and not from the action of c-myc antibodies.
 ...
PMID:c-myc protein and DNA replication: separation of c-myc antibodies from an inhibitor of DNA synthesis. 283 May 1

We have studied the transcriptional activity, steady-state mRNA levels, and steady-state protein levels of the c-myc and transferrin receptor (TfR) genes in murine M1 myeloid leukemia cells arrested in G1 phase of the cell cycle by different methods. When cells are growth-arrested by density inhibition, a technique that places the majority of cells in early G1, c-myc protein, as detected by Western analysis, is expressed at 80% of the level seen in proliferating cells. Steady-state mRNA levels and, to a lesser extent, transcriptional activity of the c-myc gene, parallel the protein findings. Under these conditions, TfR gene expression is much lower than in normally cycling cells. We have previously demonstrated that density-inhibited M1 cells, released from density inhibition and treated with the DNA polymerase alpha inhibitor aphidicolin, remain in G1, but at a point temporally closer to S phase. Cells treated in this manner demonstrate reduced transcriptional activity and expression of the c-myc gene, but TfR gene expression approximates the level found in proliferating cells. These data suggest that neither c-myc nor TfR gene expression is constant throughout the G1 phase of the cell cycle in M1 cells. c-myc gene expression is highest in early G1 and falls to low levels by late G1, while the reverse is true for TfR gene expression.
 ...
PMID:Differential expression of c-myc and the transferrin receptor in G1 synchronized M1 myeloid leukemia cells. 337

The protein product of oncogene c-myc is believed to be important in regulation of the cell cycle. However, its direct role in DNA synthesis has not been explored. Experiments presented here show that the addition of affinity-purified antibodies against the human c-myc protein to nuclei isolated from several types of human cells reversibly inhibited DNA synthesis and DNA polymerase activity of these nuclei. This suggests that c-myc encodes a protein that is functionally involved in DNA synthesis.
 ...
PMID:Participation of c-myc protein in DNA synthesis of human cells. 353 22

The binding of nuclear proteins to a DARC146 DNA fragment is described. The DARC146 was isolated from a complex form of DNA polymerase alpha. BrdUrd substitution experiments indicate that DARC146 can support an autonomous replication in mammalian cells. Three AAA blocks separated by 10 nucleotides were identified in the DARC146 sequence. Measuring electrophoretical mobility under appropriate conditions showed that these AAA blocks form a bent DNA. We have used a synthetic oligonucleotide covering the bent DNA to study the interaction of nuclear proteins with this DNA region. Four DNA-protein complexes with the bent DNA region were registered. One of them is formed by binding nuclear factor p65 to TCTATTA nucleotides. The molecular weight and binding site of p65 are very similar to those of c-myc protein. However, antibodies against c-myc protein exert no effect on the formation of the p65-DNA complex. We suggest that p65 is an unknown nuclear factor.
 ...
PMID:[The interaction of nuclear proteins with bent DNA located in an autonomously replicating DARC146 sequence]. 837 11