Site-specific carcinogen binding to DNA.
Site-specific carcinogen binding to DNA.
复制标题
与 DNA 结合的位点特异性致癌物。
DOI：
10.1073/pnas.81.18.5623
复制
发表时间：
1984
影响因子：
11.1
通讯作者：
M. Hogan
中科院分区：
文献类型：
--
作者：
T. Boles;M. Hogan
苯并[alpha]芘二醇环氧化物（BPDE）是一种研究充分的环境致癌物，与DNA共价结合。在这里，我们描述了一种光化学技术，使我们能够映射克隆基因序列内的BPDE结合位点。该技术是基于我们的观察，当用355 nm的激光照射时，在每个BPDE结合位点产生一个单链DNA切割。在最初的实验中，我们已经研究了这种切割在鸡成年β-珠蛋白基因克隆DNA中的分布。我们发现，BPDE结合在这个基因序列是明显的非随机。虽然几个突出的BPDE结合位点是明显的，但紧邻RNA帽位点5'的300个碱基对序列最受致癌物的攻击。该区域被认为含有重要的转录控制序列。我们讨论的可能性，序列特异性结合到这样的调控元件可能是致癌物的机制的一个重要特征。
Benzo[alpha]pyrene diol epoxide (BPDE) is a well-studied environmental carcinogen that binds covalently to DNA. Here we describe a photochemical technique that allows us to map BPDE-binding sites within cloned gene sequences. The technique is based upon our observation that, when irradiated with laser light at 355 nm, one single-strand DNA cut is produced at each BPDE binding site. In initial experiments we have studied the distribution of such cuts in cloned DNA from the chicken adult beta-globin gene. We find that BPDE binding in this gene sequence is distinctly nonrandom. While several prominent BPDE-binding sites are evident, a 300-base-pair sequence immediately 5' to the RNA cap site is most strongly attacked by the carcinogen. This region is believed to contain important transcriptional control sequences. We discuss the possibility that sequence-specific binding to such regulatory elements may be an important feature of the mechanism of the carcinogen.