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Human DNA polymerase α: predicted functional domains and relationships with viral DNA polymerases
Author(s) -
Wang Teresa S.E,
Wong Scott W.,
Korn David
Publication year - 1989
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.3.1.2642867
Subject(s) - biology , dna polymerase , primase , dna polymerase ii , polymerase , dna clamp , genetics , circular bacterial chromosome , dna polymerase i , dna , primer (cosmetics) , dna polymerase mu , microbiology and biotechnology , gene , polymerase chain reaction , reverse transcriptase , chemistry , organic chemistry
The primary sequence of human DNA polymerase α deduced from the full‐length cDNA contains regions of striking similarity to sequences in replicative DNA polymerases from Escherichia coli phages PRD1 and T4, Bacillus phage ɸ19, yeast DNA polymerase I, yeast linear plasmid pGKL1, maize S1 mitochondrial DNA, herpes family viruses, vaccinia virus, and adenovirus. The conservation of these homologous regions across this vast phylogenetic expanse indicates that these prokaryotic and eukaryotic DNA polymerases may all have evolved from a common primordial gene. Based on the sequence analysis and genetic results from yeast and herpes simplex virus studies, these consensus sequences are suggested to define potential sites that subserve essential roles in the DNA polymerase reaction. Two of these conserved regions appear to participate directly in the active site required for substrate deoxynucleotide interaction. One region toward the carboxyl‐terminus has the potential to be the DNA interacting domain, whereas a potential DNA primase interaction domain is predicted toward the amino‐terminus. The provisional assignment of these domains can be used to identify unique or dissimilar features of functionally homologous catalytic sites in viral DNA polymerases of pathogenetic significance and thereby serve to guide more rational antiviral drug design.— W ang , T. S.‐E.; W ong , S. W.; K orn , D. Human DNA polymerase α: predicted functional domains and relationships with viral DNA polymerases. FASEB J. 3: 14‐21; 1989.