Nucleosome structure controls rates of excision repair in DNA of human cells.

Abstract

EUKARYOTIC chromatin is now considered to be composed of structural units, nucleosomes (nu bodies), which consist of four pairs of histones around which DNA is coiled1–3. Approximately 200 base pairs of DNA are associated with each nucleosome, 140 base pairs are wrapped around each and a variable length of approximately 40 base pairs lies between1–3. The DNA wrapped around each nucleosome is less easily digested by micrococcal nuclease than the DNA between them, and brief periods of incubation with the enzyme allow isolation of nucleosomes as discrete particles2. The structural organisation of mammalian DNA into nucleosomes, and higher degrees of order in the packing of strings of nucleosomes into chromosomal fibres has been shown to play a major part in the control of DNA replication4,5, and transcription6. Previous studies have indicated that the accessibility of damage in DNA to repair enzymes is restricted by chromatin proteins7,8 and it is therefore likely that the repair of damaged sites in DNA is also controlled by some features of nucleosome structure and packing9. In the study described here I have measured the rates of degradation of repaired regions in mammalian DNA by micrococcal nuclease; the results suggest that the first sites of ultraviolet light-induced damage to be repaired are those in the DNA between nucleosomes and that there is little rearrangement of nucleosomes along the DNA during repair.