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Mol Biol Med. 1984 Oct;2(5):323-35.

Human DNA polymerase alpha. Compensation for heat-labile mouse DNA polymerase alpha and its gene localization on the X chromosome.


The chromosomal location of human DNA polymerase alpha gene was determined by studies on somatic cell hybrids between a temperature-sensitive mutant cell line of mouse FM3A cells and normal human lymphocytes or a line of human diploid fibroblasts derived from a patient with the fragile X syndrome. A temperature-sensitive mutant, FT20-M6, a 6-thioguanine-resistant derivative of tsFT20, has heat-labile DNA polymerase alpha. Interspecific cell hybrids between FT20-M6 and human cells grew at the non-permissive temperature, indicating that some human chromosomes can compensate for the temperature-sensitive defect of tsFT20 in mouse-human cell hybrids. Three of these hybrid clones were examined further, and were shown to contain heat-stable DNA polymerase alpha that was neutralized with human DNA polymerase alpha-specific monoclonal antibody. Subcloning and segregation tests of these hybrid clones showed a positive correlation between the expression of human DNA polymerase alpha and the presence of the human X chromosome. Two subclones, however, did not conform to this relationship: they grew at the nonpermissive temperature but not in hypoxanthine/amethopterin/thymidine medium. Detailed examination of the human chromosomes in these subclones revealed that these clones had only one human chromosome, an X chromosome with a terminal deletion of the long arm including the locus of the gene for hypoxanthine phosphoribosyltransferase (EC From these data, the functional DNA polymerase alpha gene was located on the human X chromosome.

[Indexed for MEDLINE]

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