Recent evidence suggests that modifications of nuclear proteins in chromatin may play an active role in the repair of DNA damage. One objective of this proposal is to determine if enhanced DNA repair occurs in regions of chromatin containing modified histones. A careful, systematic study will be performed to analyse the extent of repair synthesis in different modified forms of nucleosomes following different times after UV damage to detemrine if the early, rapid phase of DNA repair occurs preferentially in modified regions of chromatin. Both hyperacetylated and ADP-ribosylated nucleosomes will be examined. These studies will include both normal and repair deficient (xeroderma pigmentosum; XP) cells, and, therefore, will also allow comparisons of the repair patterns in cells of different repair capacity. Another objective is to examine both the overall levels of protein acetylation and the levels of individual acetylated species in normal and repair deficient human cells following UV damage. These studies stem from recent findings that a wave of histone hyperacetylation occurs in normal human cells immediately following UV damage, followed by a wave of hypoacetylation at longer times. Therefore, the pattern of different acetylated forms of histones will be examined during these changes to determine if specific acetylated species are formed during DNA repair. Comparisons with the different complementation groups of XP cells will be made to determine if the defect in any of these repair deficient cell types is related to the acetylation response.
|Ramanathan, B; Smerdon, M J (1989) Enhanced DNA repair synthesis in hyperacetylated nucleosomes. J Biol Chem 264:11026-34|