Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene doc-1

Takanori Tsuji, Fuh Mei Duh, Farida Latif, Nicolas C. Popescu, Drazen B. Zimonjic, Jim McBride, Kou Matsuo, Hiroe Ohyama, Randy Todd, Emi Nagata, Nagaaki Terakado, Akira Sasaki, Tomohiro Matsumura, Michael I. Lerman, David T W Wong

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

doc-1 is a putative tumor suppressor gene isolated and identified from the hamster oral cancer model. Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-1 gene. Human doc-1 cDNA is 1.6 kilobase pairs in length and encodes for a 115-amino acid polypeptide (12.4 kDa, pI 9.53). Sequence analysis showed 98% identity between human and hamster doc-1 protein sequences. DOC-1 is expressed in all normal human tissues examined. In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes. By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei. Human oral cancers in vivo did not exhibit immunostaining for DOC-1. Like murine DOC-1, human DOC-1 associates with DNA polymerase α/primase and mediates the phosphorylation of the large p180 catalytic subunit, suggesting it may be a potential regulator of DNA replication in the S phase of the cell cycle. Using a human doc-1 cosmid as a probe, human doc-1 is mapped to chromosome 12q24. We identified four exons in the entire human doc-1 gene and determined the intron-exon boundaries. By polymerase chain reaction and direct sequencing, we examined premalignant oral lesion and oral cancer cell lines and found no intragenic mutations.

Original languageEnglish
Pages (from-to)6704-6709
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number12
DOIs
Publication statusPublished - Mar 20 1998

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Cloning
Tumor Suppressor Genes
Cricetinae
Organism Cloning
Tumors
Genes
Mutation
Exons
Cells
DNA Primase
Cosmids
Phosphorylation
Polymerase chain reaction
DNA-Directed DNA Polymerase
Chromosomes
Mouth Neoplasms
Introns
Keratinocytes
Complementary DNA
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene doc-1. / Tsuji, Takanori; Duh, Fuh Mei; Latif, Farida; Popescu, Nicolas C.; Zimonjic, Drazen B.; McBride, Jim; Matsuo, Kou; Ohyama, Hiroe; Todd, Randy; Nagata, Emi; Terakado, Nagaaki; Sasaki, Akira; Matsumura, Tomohiro; Lerman, Michael I.; Wong, David T W.

In: Journal of Biological Chemistry, Vol. 273, No. 12, 20.03.1998, p. 6704-6709.

Research output: Contribution to journalArticle

Tsuji, T, Duh, FM, Latif, F, Popescu, NC, Zimonjic, DB, McBride, J, Matsuo, K, Ohyama, H, Todd, R, Nagata, E, Terakado, N, Sasaki, A, Matsumura, T, Lerman, MI & Wong, DTW 1998, 'Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene doc-1', Journal of Biological Chemistry, vol. 273, no. 12, pp. 6704-6709. https://doi.org/10.1074/jbc.273.12.6704
Tsuji, Takanori ; Duh, Fuh Mei ; Latif, Farida ; Popescu, Nicolas C. ; Zimonjic, Drazen B. ; McBride, Jim ; Matsuo, Kou ; Ohyama, Hiroe ; Todd, Randy ; Nagata, Emi ; Terakado, Nagaaki ; Sasaki, Akira ; Matsumura, Tomohiro ; Lerman, Michael I. ; Wong, David T W. / Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene doc-1. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 12. pp. 6704-6709.
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