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Biomedical subjects

J E Cleaver

Publications and source records attributed to J E Cleaver.

At least 235 records · Page 13Linked to original sources

Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective.

Homozygous xeroderma pigmentosum fibroblasts cannot repair damage to DNA bases, but can repair damage that involves chain breaks. In xeroderma pigmentosum, therefore, there is a defect in an early step in repair at which base damage is recognized and the polynucleotide chain broken enzymatically (by an endonuclease). Heterozygous fibroblasts repair base damage to normal extents. Carcinogenesis in xeroderma pigmentosum, and perhaps in some normal individuals, may be the result of somatic mutations caused by unrepaired damage.

Autoradiography↗

Repair replication and degradation of bromouracil-substituted DNA in mammalian cells after irradiation with ultraviolet light.

Ultraviolet (UV) light irradiation of HeLa cells in which bromouracil (BU) is substituted for thymine in one strand of the DNA, elicits a number of responses that occur predominantly in the BU strand. A small amount of degradation of both strands occurs, but the BU strand is degraded to a greater extent than the normal strand. Large UV doses (1000 erg/mm(2)) induce degradation of about 1.7% of the DNA within 6 hr of irradiation of unsubstituted cells; in BU-substituted cells under these conditions about 1.9% of the normal strand is degraded but 17.5% of the BU strand. After irradiation fresh bases are inserted into the BU strands at infrequent intervals throughout the DNA and this is presumed to represent repair of UV damage in the BU strands. After 1000 erg/mm(2) the majority (70%) of the thymidine incorporated enters the BU strand. Inhibitors of normal DNA synthesis, hydroxyurea and arabinosyl cytosine, do not appear to inhibit the repair of DNA. The increased sensitivity of mammalian cells that contain BU to irradiation may consequently be due to damage of the BU strand. A specific interference between BU and repair of DNA which leads to large amounts of DNA degradation in bacteria, does not seem to be important in the sensitization of mammalian cells with BU.

Bromodeoxyuridine↗