POLN, a Nuclear PolA Family DNA Polymerase Homologous to the DNA Cross-link Sensitivity Protein Mus308

The Drosophila Mus308 gene is unusual in encoding both a family A DNA polymerase domain and a DNA/RNA helicase domain. A mus308 mutation was shown to result in increased sensitivity to DNA cross-linking agents, leading to the hypothesis that Mus308 functions in the repair of DNA interstrand cross-li...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-08, Vol.278 (34), p.32014-32019
Main Authors: Marini, Federica, Kim, Nayun, Schuffert, Anthony, Wood, Richard D.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Chromosome Mapping
DNA - metabolism
DNA Polymerase I - chemistry
DNA Polymerase I - genetics
DNA Polymerase I - metabolism
DNA Primers
DNA Repair Enzymes
DNA-Directed DNA Polymerase
Drosophila Proteins
Humans
Male
Mice
Molecular Sequence Data
Sequence Homology, Amino Acid
Testis - enzymology
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Summary:The Drosophila Mus308 gene is unusual in encoding both a family A DNA polymerase domain and a DNA/RNA helicase domain. A mus308 mutation was shown to result in increased sensitivity to DNA cross-linking agents, leading to the hypothesis that Mus308 functions in the repair of DNA interstrand cross-links. Recently a mammalian ortholog of Mus308, POLQ, has been identified. We report here the identification, cloning, and characterization of POLN and its gene product, a new mammalian DNA polymerase also related to Mus308. The human cDNA encodes a protein of 900 amino acid residues. The region starting from residue 419 shares 33% identity (48% similarity) with the equivalent region of Escherichia coli DNA polymerase I. POLN is expressed in human cell lines with numerous alternatively spliced transcripts, and a full-length human coding region that comprises 24 exons within 160 kilobases of genomic DNA. Expression analysis by northern blotting and in situ hybridization showed highest expression of full-length POLN in human and mouse testis. POLN localized to the nucleus when expressed as a enhanced green fluorescent protein (GFP)-tagged protein in human fibroblasts. GFP-tagged recombinant POLN had DNA polymerase activity on activated calf thymus DNA and on a singly primed template.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M305646200