DNA damage in the nucleosome core is refractory to repair by human excision nuclease

To investigate the effect of nucleosomes on nucleotide excision repair in h umans, we prepared a mononucleosome containing a (6-4) photoproduct in the nucleosome core and examined its repair with the reconstituted human excisi on nuclease system and with cell extracts. Nucleosomal DNA is repaired at a rate of about 10% of that for naked DNA in both systems. These results are in agreement with in vivo data showing a considerably slower rate of repai r of overall genomic DNA relative to that for transcriptionally active DNA. Furthermore, our results indicate that the first-order packing of DNA in n ucleosomes is a primary determinant of slow repair of DNA in chromatin.