DAMAGE OF HUMAN CHROMATIN BY CARCINOGENS

本提案的总体目标是确定 不同类别的环境相关 致癌物形成不同的DNA加合物光谱， 在人体不同结构区域内的分布 染色质，以及这些加合物是否改变了 在染色质的不同结构状态之间 光纤 具体而言，我们计划：（1）表征 形成的DNA和蛋白质加合物的分布和类型 长染色质内不同种类的致癌物 模拟不同结构状态的体外片段 和组成的染色质纤维在体内;（2）确定 染色质纤维结构是否可以被改变， 不同类别致癌物形成加合物;（3） 确定这种改变是否影响结构 染色质纤维的过渡;和（4）使用这些受损的， “模型”染色质纤维作为损伤特异性的底物 体外核酸内切酶。 这些研究应该为 对DNA加合物的作用进行仔细系统的分析 染色质纤维结构和染色质纤维 组合物对切除修复酶的能力的影响 体外

The broad objective of the present proposal is to determine whether different classes of environmentally-relevant carcinogens form different DNA adduct spectrums and distributions within the different structural regions of human chromatin, and whether these adducts alter the transitions between the different structural states of the chromatin fiber. Specifically, we plan to: (1) characterize the distribution and types of DNA and protein adducts formed by different classes of carcinogens within long chromatin fragments in vitro that mimic the different structural states and compositions of the chromatin fiber in vivo; (2) determine whether the chromatin fiber structure can be altered by the formation of adducts from different classes of carcinogens; (3) determine whether such alterations affect the structural transitions of the chromatin fiber; and (4) use these damaged, "model" chromatin fibers as substrates for damage specific endonucleases in vitro. These studies should lead the way for a careful, systematic analysis of the effects of DNA adduct variation, chromatin fiber structure and chromatin fiber composition on the competency of excision repair enzymes in vitro.