Leadon S A, Hanawalt P C
Carcinogenesis. 1984 Nov;5(11):1505-10. doi: 10.1093/carcin/5.11.1505.
Excision repair of bulky adducts in alpha DNA of African green monkey cells has previously been shown to be deficient relative to that in the overall genome. We have found that u.v. irradiation of these cells results in the enhanced removal of both aflatoxin B1 (AFB1) and acetylaminofluorene (AAF) adducts from the alpha DNA sequences without affecting repair in the bulk of the DNA. The degree of enhanced removal of AFB1 is dependent upon the u.v. dose and the time interval between irradiation and AFB1 treatment. The u.v. enhancement is not inhibited by cycloheximide. Exposure of the cells to dimethylsulfate or gamma-rays does not affect AFB1 adduct repair. The formation and removal of N-acetoxy-2-acetylaminofluorene (NA-AAF) adducts from alpha and bulk DNA was studied in detail. A higher initial level of the acetylated C8 adduct of guanine was found in alpha DNA than in bulk DNA. Although both the acetylated and deacetylated C8 adducts were removed from the two DNA species, the level of repair was significantly greater in the bulk DNA. Irradiation of cells with u.v. prior to treatment with NA-AAF enhanced the removal of both adducts from alpha DNA with little or no effect on repair in bulk DNA. We conclude that the presence of u.v. photoproducts or some intermediate in their processing alters the chromatin structure of alpha DNA thereby rendering bulky adducts accessible to repair enzymes. In addition, the differential formation and repair of AAF adducts in alpha DNA compared with that in the bulk of the genome supports the hypothesis of an altered chromatin structure for alpha domains.
先前的研究表明,非洲绿猴细胞α-DNA中大分子加合物的切除修复相对于整个基因组而言是不足的。我们发现,紫外线照射这些细胞会导致从α-DNA序列中增强去除黄曲霉毒素B1(AFB1)和乙酰氨基芴(AAF)加合物,而不会影响大部分DNA的修复。AFB1增强去除的程度取决于紫外线剂量以及照射与AFB1处理之间的时间间隔。紫外线增强作用不受环己酰亚胺的抑制。将细胞暴露于硫酸二甲酯或γ射线不会影响AFB1加合物的修复。我们详细研究了α-DNA和大部分DNA中N-乙酰氧基-2-乙酰氨基芴(NA-AAF)加合物的形成和去除。发现α-DNA中鸟嘌呤的乙酰化C8加合物的初始水平高于大部分DNA中的水平。尽管乙酰化和脱乙酰化的C8加合物都从这两种DNA中被去除,但大部分DNA中的修复水平明显更高。在用NA-AAF处理之前用紫外线照射细胞,增强了从α-DNA中去除两种加合物的能力,而对大部分DNA的修复几乎没有影响。我们得出结论,紫外线光产物或其加工过程中的某些中间体的存在改变了α-DNA的染色质结构,从而使大分子加合物能够被修复酶识别。此外,与基因组大部分区域相比,α-DNA中AAF加合物的差异形成和修复支持了α结构域染色质结构改变的假说。