DNA polymerase δ: gene sequences fromPlasmodium falciparumindicate that this enzyme is more highly conserved than DNA polymerase α

Abstract

Genes encoding proteins homologous to the catalytic subunits of DNA polymerase alpha and delta have been cloned from the human malaria parasite Plasmodium falciparum. These are among the first cellular replicative DNA polymerase genes to be cloned and their sequences allow us to make new statements about the relative degrees of conservation of these two enzymes. The most important finding was that P. falciparum Pol delta showed considerable homology to the only other Pol delta enzyme for which published sequence is available, that of S. cerevisiae, displaying an overall amino acid identity of 45% and identity over a highly conserved central region of 59%. In contrast, the level of identity shown over the equivalent central region of Pol alpha between the P. falciparum and S. cerevisiae sequences is only 32%. The sequence data also allowed us to examine the degree of conservation in putative exonuclease domains of Pol delta. The Pol delta gene of P. falciparum maps to chromosome 10 and evidence is presented for the presence of different sized Pol delta mRNA's in the asexual and sexual erythrocytic stages of parasite development.

The Human POLD1 Gene

“…In addition, the coding sequences of the pol ␦ catalytic subunit have been isolated from bakers' yeast (13), fission yeast (14), malaria parasite (15,16), calf thymus (17), and mouse cells (18). Sequence analysis showed that the catalytic subunit of human pol ␦ contains 1,107 amino acids and is related to other eukaryotic DNA polymerases (11).…”

Plasmodium falciparum origin recognition complex subunit 5: functional characterization and role in DNA replication foci formation

“…The biochemistry and enzymology of nuclear Plasmodium DNA replication has been restricted to the cloning and characterization of some replication factors like PfORC1, PfMCMs (mini-chromosome-maintenance proteins), PfPCNA, PfRPA and few DNA polymerase enzymes (Ridley et al, 1991;Kilbey et al, 1993;Patterson et al, 2002;Voss et al, 2002;Mehra et al, 2005;Gupta et al, 2006;Patterson et al, 2006;Nunthawarasilp et al, 2007). Few Plasmodium homologues of cyclins and cdk-like kinases have been reported (Doerig et al, 2002;Ward et al, 2004).…”

Plasmodium falciparum Possesses a Cell Cycle-regulated Short Type Replication Protein A Large Subunit Encoded by an Unusual Transcript

“…Most of the studies on DNA replication in P. falciparum have been conducted during the erythrocytic stages. Several genes involved in eukaryotic chromosomal DNA replication and their encoded proteins have been identified in this parasite, including DNA polymerases ␣ (DNA pol ␣) 1 (1,2) and ␦ (DNA pol ␦) (3,4), proliferating cell nuclear antigen (5), and topoisomerases I (6) and II (7). It has been shown that expression of these genes follows a stagespecific pattern coinciding with the beginning of chromosomal replication which starts 28 -31 h after merozoite invasion and continues through most of schizogony (8).…”