How are potent bulky carcinogens able to induce such a diverse array of mutations?
How are potent bulky carcinogens able to induce such a diverse array of mutations?
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强效大体积致癌物如何能够诱导如此多样化的突变？
DOI：
10.1002/mc.2940130404
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发表时间：
1995
影响因子：
4.6
通讯作者：
Loechler,EL
中科院分区：
文献类型：
--
作者：
Loechler,EL
通过使用随机和加合物位点特异性诱变方法，研究了大肠杆菌中活化苯并[a]芘（+）-抗-B[a]PDE）诱导的突变。提出了一个工作假设，即（+）-抗-B[a]PDE的主要加合物（在N2-Gua处形成）能够诱导不同的碱基取代突变（例如，GC→TA vs. GC→AT）取决于其在DNA中的构象，这可能受各种因素的影响，特别是DNA序列背景。移码突变在（+）-抗B[a]PDE中也很常见，其他研究表明移码和碱基置换诱变途径是偶联的。使这种相互关系合理化的最简单的假设是，单一构象的单一（+）-抗BEa[a]PDE加合物可以通过移码或碱基取代途径绕过。如果在诱变途径上存在两种不同的构象，则可以调和这种违反直觉的概念：I类构象，其是双链DNA中的DNA加合物在遇到DNA聚合酶之前的初始构象，以及II类构象，其是在DNA聚合酶复制期间在单链/双链DNA连接处形成的构象。因此，GC→TA和GC→AT突变可能由不同的I类构象诱导，而碱基取代和移码突变可能由相同的I类构象但不同的II类构象诱导。诱变的途径将由相关的I类和II类构象决定，而这又将由各种因素控制，特别是DNA序列背景。© 1995 Wiley利斯公司
Mutations induced by activated benzo[a]pyrene ((+)‐anti‐B[a]PDE) in Escherichia coli are being investigated, by using both random and adduct‐site–specific mutagenesis approaches. A working hypothesis was proposed that the major adduct of (+)‐anti‐B[a]PDE (formed at N2‐Gua) is able to induce different base‐substitution mutations (e.g., GC→TA vs. GC→AT) depending upon its conformation in DNA, which can be influenced by various factors, notably DNA sequence context. Frameshift mutations are also common with (+)‐anti‐B[a]PDE, and other work suggested that the frameshift and base‐substitution mutagenesis pathways are coupled. The simplest hypothesis to rationalize this interrelationship is that a single (+)‐anti‐BEa[a]PDE adduct in a single conformation can be bypassed via either a frameshift or a base‐substitution pathway. This counterintuitive notion can be reconciled if there are two different kinds of conformations on the pathway to mutagenesis: a class I conformation, which is the initial conformation of a DNA adduct in double‐stranded DNA before its encounter with a DNA polymerase, and a class II conformation, which is the conformation that forms at a single‐strand/double‐strand DNA junction during replication by a DNA polymerase. Thus, GC→TA and GC→AT mutations may be induced by different class I conformations, whereas base substitution and frameshift mutations may be induced by the same class I conformation but by different class II conformations. The pathway of mutagenesis would be dictated by the relevant class I and II conformations, which in turn would be controlled by various factors, notably DNA sequence context. © 1995 Wiley‐Liss, Inc.
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位点特异性诱变：回顾性和前瞻性。
影响因子：
4.7
作者：
Singer,B;Essigmann,JM
通讯作者：
Essigmann,JM
构建含有在指定位点的 ( )-抗二苯并[a,j]蒽二醇环氧化物的脱氧腺苷和脱氧鸟苷加合物的大肠杆菌载体。
影响因子：
4.1
作者：
Gill,RD;Min,Z;Cortez,C;Harvey,RG;Loechler,EL;DiGiovanni,J
通讯作者：
DiGiovanni,J
DOI：
10.1073/pnas.89.5.1914
发表时间：
1992-03-01
影响因子：
11.1
作者：
COSMAN, M;DELOSSANTOS, C;PATEL, DJ
通讯作者：
PATEL, DJ
AP位点并不显着参与苯并[a]芘的( )-抗二醇环氧化物的诱变：其诱变特异性的复杂性可能是由加合物构象多态性引起的。
影响因子：
2.9
作者：
Drouin,EE;Loechler,EL
通讯作者：
Loechler,EL
影响因子：
2.9
作者：
COSMAN, M;DELOSSANTOS, C;PATEL, DJ
通讯作者：
PATEL, DJ