Selby C P, Sancar A
Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill 27599.
Proc Natl Acad Sci U S A. 1990 May;87(9):3522-5. doi: 10.1073/pnas.87.9.3522.
Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.
咖啡因可增强基因毒性剂的诱变和致死效应。据认为，至少在某些生物体中，这是由于DNA修复受到抑制所致。然而，一直缺乏抑制修复酶的直接证据。我们使用纯化的大肠杆菌DNA光解酶和（A）BC切除核酸酶，证明该药物通过两种不同机制抑制光复活和核苷酸切除修复。咖啡因通过干扰光解酶与受损DNA的特异性结合来抑制光复活，并且通过促进（A）BC切除核酸酶的损伤识别亚基UvrA的非特异性结合来抑制核苷酸切除修复。许多其他嵌入剂，包括吖啶黄素和溴化乙锭，似乎通过类似的机制抑制切除核酸酶——也就是说，通过将UvrA亚基捕获在未受损DNA上的非生产性复合物中。
