Nucleosomal rearrangement

Ultimately the DNA lesion is repaired by a short patch repair mechanism, which, in linker regions of nucleosomes or open regions of chromatin (where lesions are generally concentrated) is associated with minimal nucleosome rearrangement (Jones et al, 2001). 

TempoM Relationship of Nucleosomal Rearrangement to Individual Steps in DNA Excision Repair... 

Thibeault L, Hengartner M, Lagueux J, Poirier G, Muller S (1992) Rearrangements of the nucleosome structure in chromatin by poly (ADP-ribose). Biochim Biophys Acta 1121 317-324 Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410 227—230... 

The two models for HMGN action are not mutually exclusive, as HMGN may use both mechanisms to alter chromatin structure. Several observations point to an interplay between linker histones and the core histone tails. For example, linker histone inhibits the acetylation of H3 by P/CAF [93]. The inhibition was shown to result from steric hindrance of the tail by linker histones, rather than tail inaccessibility due to chromatin folding. It has also been shown that the removal of core histone tails may reduce the affinity of linker histone HI for the nucleosome [94], and that the interaction of the C-terminal tail of core histone H2A with linker DNA is rearranged in the presence of HI [47]. It is conceivable, therefore, that HMGN modulates the activity both of the core histone tails and of linker histones within the same nucleosome. 

The elastic stress may be external or internal. External stresses are exerted on the chromatin during the cell cycle when the mitotic spindle separates chromosome pairs. The 30-nm fiber should be both highly flexible and extensible to survive these stresses. The in vitro experiments by Cui and Bustamante demonstrated that the 30-nm fiber is indeed very soft [66]. The 30-nm fiber is also exposed to internal stresses. Attractive or repulsive forces between the nucleosomes will deform the linkers connecting the nucleosomes. For instance, electrostatic interactions, either repulsive (due to the net charge of the nucleosome core particles) or attractive (bridging via the lysine-rich core histone tails [49]) could lead to considerable structural rearrangements. 

The rate of formation of cisplatin-DNA adducts was found to be independent of superhelicity [59] and appears to be unaffected by the presence of histones in nucleosomes [29] and in chromatin [77], Therefore, isolated DNA in aqueous solution appears to be a relevant model for kinetic and mechanistic studies of cellular DNA-platination. It was early checked that the cisplatin-DNA adducts were stable for a least three days at 37 °C after their formation [78], There are now a few cases reported of unstable platinum adducts (vide supra) i) monoadducts with the diazapyrenium ligand [52], ii) a cisplatin intrastrand GG chelate rearranging into a GG interstrand crosslink [63], iii) cisplatin GG interstrand diadducts, slowly rearranging into intrastrand ones [65], tv) transplatin intrastrand GNG diadducts rearranging into interstrand crosslinks (J.-M. Malinge and M. Leng, Part 3). 

Table 2). Again, these data suggest that rearrangement of newly synthesized repair patches relative to the nucleosomal organization of chromatin is dependent on nuclear ADP-ribosylation activity. 

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