Infidelity of DNA synthesis by reverse transcriptase.
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Biomedical subjects
Publications and source records attributed to L A Loeb.
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Evidence is presented that DNA polymerases from human leukemic cells are mutagenic. Nucleic acid-free extracts of acute lymphoblastic leukemic cells polymerized about 10-times more dCTP using poly(dA-dT).poly(dA-dT) as a template than did extracts from normal lymphocytes. Mutagenic DNA polymerases could perhaps play an important role in tumor progression.
The requirement for Zn(++) in DNA replication by phytohemagglutinin-stimulated human lymphocytes was studied. When 6 microM o-phenanthroline, a chelator with a high affinity for Zn(++), is added to cultures of stimulated lymphocytes a nearly complete inhibition of thymidine incorporation results within a few hours. In contrast, the incorporation of uridine is only slightly reduced and the incorporation of leucine is unaffected. m-Phenanthroline, a nonchelating analogue, does not alter the rate of thymidine incorporation even when present in 10-fold greater amounts than o-phenanthroline. The inhibition of thymidine incorporation by o-phenanthroline could be entirely reversed by the addition of Zn(++) to the cultures, or could be prevented by the prior addition of either Zn(++) or Ni(++). All other divalent cations tested were incapable of reversing the o-phenanthroline inhibition of thymidine incorporation.
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