SELECTIVE REPAIR OF SPECIFIC CHROMATIN DOMAINS IN UV-IRRADIATED CELLS FROM XERODERMA-PIGMENTOSUM COMPLEMENTATION GROUP-C

The limited DNA-excision repair in UV-irradiated nondividing fibroblasts from xeroderma pigmentosum complementation group C (XP-C) occurs in localized chromatin regions generating large DNA segments (at least 30-70 kb) free of pyrimidine dimers. A genomic fraction enriched for this DNA was isolated on the basis of the larger size of the repaired fragments after UV-endonuclease treatment and screened for specific genes. It contains more copies per μg DNA of two transcriptionally active genes, β-actin and dihydrofolate reductase, compared to the remaining DNA but an equal number of copies per μg DNA of an inactive locus termed 754. We confirmed that the active genes were preferentially repaired by measuring the removal of pyrimidine dimers from specific genomic restriction fragments comprising these sequences. These results mean that a unique set of relatively large chromatin domains are repaired in nondividing XP-C cells, even though most of the DNA remains unrepaired. The repaired domains may be those containing the active genes. This specific repair may account for the relatively high UV-resistance of the nondividing cells. In normal cells, a very rapid repair of a restriction fragment containing the β-actin gene and slow repair of the 754-containing fragment was detected indicating that a similar domain-oriented repair process also exists in these cells. These results are consistent with the previously discovered rapid repair of active genes compared to bulk DNA. Separate damage-recognition systems may exist in human cells for chromatin domains that contain transcribed regions and those that contain no transcribed regions. The latter system may be deficient in XP-C. © 1990.