Does radial nuclear organisation influence DNA damage?
It has been suggested that chromatin at the nuclear periphery could act to shield DNA sequences in the nuclear interior from damage. To test this hypothesis, we have examined the nuclear distribution of sites of DNA repair induced by oxidation or UV-C. We do not detect more damage (repair) at the nuclear periphery than in the nuclear interior. In fact, contrary to the body guard hypothesis, there is an excess of damage detected in the nuclear interior. This is further supported by sequence comparison between genes on human chromosomes 18 or 19, and their counterparts in the chimpanzee. The synonymous substitution rate for genes on chromosome 19, which is located towards the centre of the human nucleus, was higher than that for genes on chromosome 18, which is located at the nuclear periphery. We conclude that chromatin at the periphery of the human nucleus is not able to protect more internally located sequences from damage and mutation. We suggest that features of the chromatin structure, or base composition, of sequences in the nuclear centre make them more susceptible to damage.
Gazave
Elodie
E
MRC Human Genetics Unit, Crewe Road, Edinburgh, EH4 2XU, UK.
Gautier
Philippe
P
Gilchrist
Susan
S
Bickmore
Wendy A
WA
D045744:Cell Line, Tumor; D045584:Chromosome Positioning; D002887:Chromosomes, Human, Pair 18 / Q000378:metabolism*; D002888:Chromosomes, Human, Pair 19 / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D004260:DNA Repair; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016296:Mutagenesis / Q000235:genetics; D018384:Oxidative Stress; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D006861:Hydrogen Peroxide