Aguirrezabalaga I, Sierra L M, Comendador M A
Departamento de Biología Funcional, Universidad de Oviedo, Spain.
Mutat Res. 1995 May;336(3):243-50. doi: 10.1016/0921-8777(94)00057-d.
The hypersensitivity of the mus308 mutant of D. melanogaster to cross-linking agents has been suggested to be the consequence of a possible defect of this mutant in DNA cross-link repair. Moreover, the mus308 mutation has been proposed as an animal model for the study of Fanconi's anemia. In order to obtain more information about the function controlled by this locus, we have measured the mutability of the mus308 mutant to several mutagens with different modes of action using the sex-linked recessive lethal test. We show that this mutation confers hypermutability not only to the cross-linking agents tested, hexamethylphosphoramide and hexamethylmelamine, but to the point mutagen N-ethyl-N-nitrosourea as well, whereas the response to methyl methanesulfonate was normal. The results suggest that the mus308 locus is not defective in a repair pathway specific for cross-links but is rather involved in a step of a more general post-replication repair process responsible for the removal of non-excised adducts.
黑腹果蝇的mus308突变体对交联剂的超敏性被认为是该突变体在DNA交联修复中可能存在缺陷的结果。此外，mus308突变已被提议作为研究范可尼贫血的动物模型。为了获得更多关于该基因座所控制功能的信息，我们使用性连锁隐性致死试验，测定了mus308突变体对几种具有不同作用方式的诱变剂的突变率。我们发现，这种突变不仅使所测试的交联剂六甲基磷酰胺和六甲基三聚氰胺产生超突变性，而且使点突变剂N-乙基-N-亚硝基脲也产生超突变性，而对甲基磺酸甲酯的反应则正常。结果表明，mus308基因座在交联特异性修复途径中没有缺陷，而是参与了一个更普遍的复制后修复过程的步骤，该过程负责去除未切除的加合物。
