Premium
Nonrandom AP site distribution in highly proliferative cells
Author(s) -
Chastain Paul D.,
Nakamura Jun,
Swenberg James,
Kaufman David
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6145fje
Subject(s) - ap site , dna , microbiology and biotechnology , dna damage , guanine , biology , reactive oxygen species , chromatin , chemistry , genetics , gene , nucleotide
Reactive oxygen species (ROS) and the oxidative DNA damage they produce [e.g., 8‐oxo‐guanine and apurinic/apyrimidinic (AP) sites] have been linked to the pathogenesis of several age‐related and chronic diseases. The basal number of AP sites measured in DNA by immuno‐slot‐blot analysis ranges from 70,000 to 100,000 per genome. We used electron microscopy to determine how AP sites were distributed in isolated DNA fibers from fresh calf thymus and HeLa cell cultures. We observed that AP sites were not equally distributed throughout all the fibers. A small percentage of the analyzed DNA fibers contained a disproportionate amount of the total AP sites in nonrandom groups of 10 to >30 closely spaced in a small region ( e.g. , 20 AP sites in a 6 kb length of DNA). This fisuggests that genomic sites may differ in their vulnerability to ROS damage, perhaps because of local chromatin structure. Nonrandom AP site formation also suggests that the detrimental effects of ROS in the development of disease may be related not simply to the total number of AP sites present but to how AP sites are distributed along a DNA fibers and, perhaps, to the genomic sites affected.—Chastain, II, P. D., Nakamura, J., Swenberg, J., Kaufman, D. Nonrandom AP site distribution in highly proliferative cells. FASEB J. 20, E2127–E2132 (2006)