DNA damage can alter the stability of nucleosomes: Effects are dependent on damage type.
Journal Article
·
· Proceedings of the National Academy of Sciences of the United States of America
- ASSOC WESTERN UNIVERSITY
- BATTELLE (PACIFIC NW LAB)
- VISITORS
We have investigated the effects of DNA damage by (±)-anti-benzo[a]pyrene diol epoxide (BPDE) and UV light on the formation of a positioned nucleosome in the Xenopus borealis 5S rRNA gene. Gel-shift analysis of the reconstituted products indicates that BPDE damage facilitates the formation of a nucleosome onto this sequence. Competitive reconstitution experiments show that average levels of 0.5, 0.9, and 2.1 BPDE adducts/146 bp of 5S DNA (i.e., the size of DNA associated with a nucleosome core particle) yield changes of -220, -290, and -540 cal/mol, respectively, in the free energy (?G) of nucleosome formation. These values yield increases of core histone binding to 5S DNA (Ka) of 1.4-, 1.6-, and 2.5-fold, compared with undamaged DNA. Conversely, irradiation with UV light decreases nucleosome formation. Irradiation at either 500 or 2500 J/m2 of UV light [0.6 and 0.8 cyclobutane pyrimidine dimer/146 bp (on average), respectively] results in respective changes of +130 and +250 cal/mol. This translates to decreases in core histone binding to irradiated 5S DNA (Ka) of 1.2- and 1.5-fold compared with undamaged DNA. These results indicate that nucleosome stability can be markedly affected by the formation of certain DNA lesions. Such changes could have major effects on the kinetics of DNA processing events.
- Research Organization:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1525973
- Report Number(s):
- PNNL-SA-28501
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 6 Vol. 94
- Country of Publication:
- United States
- Language:
- English
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