title: DNA repair and replication in xeroderma pigmentosum and related disorders.
abstract: Xeroderma pigmentosum (XP), ataxia telangiectasia (AT), and Cockayne syndrome (CS) are human diseases that exhibit increased sensitivity to environmental carcinogens [e.g., ultraviolet (UV) light, ionizing radiations, chemicals] because of genetic defects in the patient's capacity to repair and replicate damaged DNA accurately. The major defect in XP is a failure to repair UV damage to DNA; in AT, the failure is in repair or replication of double-strand breaks in DNA; in CS, the failure is in recovery of DNA replication after UV irradiation. Cancer is a major clinical feature of XP and AT, but not of CS. Each disease is complex, with multiple groups defined by complementation in cell-cell hybridization. Overlap is reported between some XP and CS groups. UV-sensitive hamster cell mutants are also known: most of these complement XP groups, and a human gene on chromosome 19 can correct the defects in hamster mutants, but not XP. XP group C is distinct from the other groups in exhibiting a strongly clustered mode of repair, as if only certain regions of the genome can be mended. This mode mainly occurs in confluent group C cells under conditions that permit much greater survival than in exponential growth, and therefore represents a more efficient mode of repair. These diseases all represent important examples of perturbation in the way carcinogen damage in DNA is metabolized, and further research aimed at identifying the kinds of molecular changes involved in the malignancy will be important.
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D003057:Cockayne Syndrome / Q000235:genetics*; D004260:DNA Repair; D004261:DNA Replication; D004392:Dwarfism / Q000235:genetics*; D006801:Humans; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000378:metabolism