The endogenous nuclease sensitivity of repaired DNA in human fibroblasts.
The limited DNA excision repair that occurs in the chromatin of UV-irradiated growth arrested cells isolated from a xeroderma pigmentosum (XP) complementation group C patient is clustered in localized regions. The repaired DNA was found to be more sensitive to nicking by endogenous nucleases than the bulk of the DNA. The extra-sensitivity does not change with increasing amounts of DNA damage or repair activity in the locally-repaired regions and is retained through a 24-h chase period. We suggest that these results are due to the occurrence of DNA repair limited to pre-existing, non-transient chromatin fractions that contain actively transcribed DNA. A similar extra-sensitivity of repaired DNA was not detected in cells of normal or XP complementation group A strains that exhibit either normal or limited repair located randomly throughout their genomes. The association between endogenous nuclease sensitivity and clustered repair probably defines a normal excision repair pathway that is specific for selected chromatin domains. The repair defect in XP-C strains may be one in pathways targeted for other endogenous nuclease-resistant domains.
D002467:Cell Nucleus / Q000201:enzymology; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000528:radiation effects; D004260:DNA Repair; D003851:Deoxyribonucleases / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007700:Kinetics; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D002843:Chromatin; D004247:DNA; D003851:Deoxyribonucleases