Divalent ions attenuate DNA synthesis by human DNA polymerase α by changing the structure of the template/primer or by perturbing the polymerase reaction

•Mg2+ at suboptimal concentration inhibited DNA polα and several other pols on templates with repetitive sequence by stabilizing unconventional DNA structure(s).•Zn2+ supported DNA synthesis reactions by polα with low efficiency, but inhibited synthesis when Mg2+ was present, suggesting the possibility that the step of removal of divalent metal ions after the formation of the phosphodiester bond is critical for polymerase reaction.•The balance of the divalent metal ions is critical for the efficient DNA polymerase function.