Comparison of DNA Polymerases α and 8 δfrom Bone Marrow

DNA polymerases α and δ from rabbit bone marrow were purified to specific activities greater than 30 000 nM TMP incorporated (mg of protein)^-1 h^-1. α is quantitatively predominant, α and δ have the same reaction requirements and are both similarly sensitive to N-ethylmaleimide. The primary functional distinction is the association of 3′ to 5′ exonuclease activity with δ. Sedimentation coefficients obtained from zone sedimentation in glycerol gradients and Stokes radii values from gel filtration allow the calculation of true molecular weight and frictional ratios, α exhibits a bimodal pattern, sedimenting at 6 and 8 S on glycerol gradients and demonstrating components corresponding to 40.5- and 65-Å Stokes radii upon gel filtration. The calculated molecular weights of the two forms of α are 100 000 and 215 000; the frictional ratios are 1.34 and 1.65. This and other data suggest a possible monomer-dimer relation. In contrast, δ sediments uniformly at 6.5 S and also behaves uniformly upon gel filtration at 45.5 A. The molecular weight of δ is distinct at 122 000; its frictional ratio is 1.39. Because of similarities of the DNA polymerizing activities of both forms of α and of d, it is postulated that α is derived from δ by structural modification, resulting in a decrease in molecular weight, the tendency to aggregate as dimers, and a concomitant loss of 3′ to 5′ exonuclease activity.