TY - JOUR
T1 - Distribution of DNA damage in chromatin and its relation to repair in human cells treated with 7-bromomethylbenz(a) anthracene
AU - Oleson, Frederick B.
AU - Mitchell, Bonnie L.
AU - Dipple, Anthony
AU - Lieberman, Michael W.
N1 - Funding Information:
1. Thi s study was supported by NIH Grant CA 20513 and by the following com-
Funding Information:
Phili p Morris, Inc.; Lorillard, a Division of Loews Theatres, Inc.; Liggett s Myers, Inc.; R.J. Reynolds Tobacco Co.; United States Tobacco Co.; and Tobacco Associates, Inc. Media and cells were provided by the Washington University Cancer Center (supported by NIH Grant CA 16217) .
Funding Information:
2. Recipient of NIH Postdoctoral Fellowship CA 09118. Present addressi Divi-sion of Medicine and Environmental Health, Monsanto Company, St. Louis,
Funding Information:
Additiona l support was provided by NCI under contract NO1-CO-75380 with Litton Bionetics, Inc.
PY - 1979/11/10
Y1 - 1979/11/10
N2 - We have examined the relationship between the distribution of DNA damage and repair in chromatin from confluent human fibroblasts treated with the carcinogen 7-bromomethy lbenz (a)anthracene. Analysis of staphylococcal nuclease (SN)4 digestion kinetics and gel electrophoresis revealed that more total damage occurs in nucleosome core DNA (∼80-85% of chromatin DNA) than in SN sensitive DNA (∼15-20%). Furthermore, over a 24 hr period, damage is removed at about the same rate from these two regions. In contrast, virtually all of the nucleotides incorporated during repair synthesis are initially SN sensitive even when measured at 12 hr after damage. With time many repair-incorporated nucleotides become SN resistant and coelectrophorese with nucleosome core DNA. To explain these data we propose a model whereby excision repair occurs in both linker and core DNA, however, in core DNA the repair process induces conformational changes resulting in temporarily increased SN sensitivity; subsequently, rearrangement occurs and results in the re-establishment of native or near-native nucleosome conformation and SN resistance.
AB - We have examined the relationship between the distribution of DNA damage and repair in chromatin from confluent human fibroblasts treated with the carcinogen 7-bromomethy lbenz (a)anthracene. Analysis of staphylococcal nuclease (SN)4 digestion kinetics and gel electrophoresis revealed that more total damage occurs in nucleosome core DNA (∼80-85% of chromatin DNA) than in SN sensitive DNA (∼15-20%). Furthermore, over a 24 hr period, damage is removed at about the same rate from these two regions. In contrast, virtually all of the nucleotides incorporated during repair synthesis are initially SN sensitive even when measured at 12 hr after damage. With time many repair-incorporated nucleotides become SN resistant and coelectrophorese with nucleosome core DNA. To explain these data we propose a model whereby excision repair occurs in both linker and core DNA, however, in core DNA the repair process induces conformational changes resulting in temporarily increased SN sensitivity; subsequently, rearrangement occurs and results in the re-establishment of native or near-native nucleosome conformation and SN resistance.
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U2 - 10.1093/nar/7.5.1343
DO - 10.1093/nar/7.5.1343
M3 - Article
C2 - 514816
AN - SCOPUS:0018770305
SN - 0305-1048
VL - 7
SP - 1343
EP - 1362
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 5
ER -