首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Probing the effects of DNA-protein interactions on DNA hole transport: the N-terminal histone tails modulate the distribution of oxidative damage and chemical lesions in the nucleosome core particle
Authors:Davis William B  Bjorklund Chad C  Deline Marshall
Institution:School of Molecular Biosciences, Biotechnology/Life Sciences 135, Washington State University, Pullman, Washington 99164-7520, USA. wbdavis@wsu.edu
Abstract:The ability of DNA to transport positive charges, or holes, over long distances is well-established, but the mechanistic details of how this process is influenced by packaging into DNA-protein complexes have not been fully delineated. In eukaryotes, genomic DNA is packaged into chromatin through its association with the core histone octamer to form the nucleosome core particle (NCP), a complex whose structure can be modulated through changes in the local environment and the histone proteins. Because (i) varying the salt concentration and removing the histone tails influence the structure of the NCP in known ways and (ii) previous studies have shown that DNA hole transport (HT) occurs in the nucleosome, we have used our previously described 601 sequence NCPs to test the hypothesis that DNA HT dynamics can be modulated by structural changes in a DNA-protein complex. We show that at low salt concentrations there is a sharp increase in long-range DNA HT efficiency in the NCP as compared to naked DNA. This enhancement of HT can be negated by either removal of the histone tails at low salt concentrations or disruption of the interaction of the packaged DNA and the histone tails by increasing the buffer's ionic strength. Association of the histone tails with 601 DNA at low salt concentrations shifts the guanine damage spectrum to favor lesions like 8-oxoguanine in the NCP, most likely through modulation of the rate of the reaction of the guanine radical cation with oxygen. These experimental results indicate that for most genomic DNA, the influence of DNA-protein interactions on DNA HT will depend strongly on the level of protection of the DNA nucleobases from oxygen. Further, these results suggest that the oxidative damage arising from DNA HT may vary in different genomic regions depending on the presence of either euchromatin or heterochromatin.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号