Interaction of human DNA polymerase β with ions of copper, lead, and cadmium

Gestational and Lactational Lead Intoxication Produces Alterations in the Hepatic System of Rat Pups

“…Lead can be concentrated in the nucleus and can perturb cell proliferation and DNA synthesis in vivo (Pepenoe and Schamaeler, 1979;Gennart et al, 1980;Coogan et al, 1994). These alterations may occur via indirect mechanisms, including disturbances of enzyme functions important in DNA repair or interference in the calcium-regulated processes of synthesis (Hartwig et al, 1990).…”

Lead Acetate Induced Cytotoxicity in Male Germinal Cells of Swiss Mice.

“…However, lead ions are known to participate in a Fenton reaction generating ROS, which can apparently cause DNAbreaks 17) . In addition, lead ions are reportedly known to inhibit the DNA polymerase β, one of the prime enzymes involved in DNA repair 18) . Hence, ROS-induced DNA alterations due to lead catalysis could not have been repaired.…”

Cancer risk from inorganics

“…Enhanced radiosensitivity has been shown following cisplatin treatment under anoxic conditions, suggesting a mechanism for the observed synergism between cisplatin and radiotherapy for anoxic tumor tissues [231]. Similarly, Popenoe and Schmaeler [192] show that inhibition of human DNA polymerase B by copper, lead, and cadmium was not affected by pretreating the enzyme with a sulfhydryl reagent. Effects of metals on another major cellular detoxification mechanism -DNA repair was discussed in section 2.2.2.…”

“…The ability of metals to bind to DNA, RNA, and protein has been well documented (for further detail, see [51,182,191]). In general, transition metals interact with DNA and polynucleotides at electron donor sites such as the oxygen and nitrogen atoms of the bases, and by complexing with the phosphate groups in the DNA backbone [182,192,193], leading to cross-linking with adjacent DNA strands, intercalation, and cross-linking with adjacent proteins. Persisting DNA-protein and metal-DNA adducts, with partial or no repair, have been demonstrated [191,194].…”

“…Direct effects of metals on DNA and RNA polymerases have also been reported frequently (reviewed by Sunderman [78]), For example, Be (II) forms a strong complex with DNA polymerase I [182]. Copper (1I), lead (II), and cadmium (II) reversibly inhibit human DNA polymerase by direct interaction with the enzyme, but not at the catalytic magnesium, manganese or zinc sites [192].…”