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 humans, we prepared a mononucleosome containing a (6-4) photoproduct in the nucleosome core and examined its repair with the reconstituted human excision 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 repair of overall genomic DNA relative to that for transcriptionally active DNA. Furthermore, our results indicate that the first-order packing of DNA in nucleosomes is a primary determinant of slow repair of DNA in chromatin.
Hara
R
R
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
Mo
J
J
Sancar
A
A
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002457:Cell Extracts; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051716:Replication Protein A; D051760:Xeroderma Pigmentosum Group A Protein
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D006657:Histones; D046911:Macromolecular Substances; D009707:Nucleosomes; D009841:Oligonucleotides; D016601:RNA-Binding Proteins; C497167:RPA1 protein, human; D051716:Replication Protein A; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human; D004247:DNA; D003851:Deoxyribonucleases