Replicative δ Polymerases from Plants and Animals Possess Very Similar Polymerase, Proofreading and Regulatory Domains

Abstract

In eukaryotes, genome replication starts with the initiation of replication by the primases, followed by the synthesis of the leading- and lagging-strands by two different replicative DNA polymerases (pols), viz. ε and δ, respectively. The polymerase and proofreading (PR) active sites of the δ pols are analyzed from various animal and plant sources by multiple sequence alignment (MSA). The animal and plant δ pols are found to possess almost identical polymerase and PR domains. However, the BLASTp analysis has shown only 56.57% identity between the plant (Arabidopsis thaliana) and animal (human) δ pols. The template-binding pair (–YG-), the catalytic amino acid (K) and the nucleotide selection amino acid (Q) are found to be the same in both plant and animal δ pols. The δ pols from plant and animal sources contain a typical Mg2+-binding motif, (-YGDTD-) in the polymerase domain and 2 possible Zn2+-binding motifs (ZBMs) in their carboxy terminal domain (CTD). One of the ZBMs binds to the 4Fe-4S cluster and is suggested to be involved in the regulation of replication. Interestingly, the invariant –SLYPS- and -YGDTD- motifs which are found in the δ pols are not found in the other replicative pol ε. Furthermore, both animal and plant δ pols use the same PR exonuclease active site amino acids, and thus, belong to the DEDD(Y)-superfamily of exonucleases, as found in other DNA pols. Besides, many specialized, conserved sequence motifs are also identified and discussed.