Gerlach V L, Aravind L, Gotway G, Schultz R A, Koonin E V, Friedberg E C
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9072, USA.
Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11922-7. doi: 10.1073/pnas.96.21.11922.
To understand the mechanisms underlying mutagenesis in eukaryotes better, we have cloned mouse and human homologs of the Escherichia coli dinB gene. E. coli dinB encodes DNA polymerase IV and greatly increases spontaneous mutations when overexpressed. The mouse and human DinB1 amino acid sequences share significant identity with E. coli DinB, including distinct motifs implicated in catalysis, suggesting conservation of the polymerase function. These proteins are members of a large superfamily of DNA damage-bypass replication proteins, including the E. coli proteins UmuC and DinB and the Saccharomyces cerevisiae proteins Rev1 and Rad30. In a phylogenetic tree, the mouse and human DinB1 proteins specifically group with E. coli DinB, suggesting a mitochondrial origin for these genes. The human DINB1 gene is localized to chromosome 5q13 and is widely expressed.
为了更好地理解真核生物中诱变作用的潜在机制,我们克隆了大肠杆菌dinB基因的小鼠和人类同源基因。大肠杆菌dinB编码DNA聚合酶IV,过表达时会显著增加自发突变。小鼠和人类的DinB1氨基酸序列与大肠杆菌DinB具有显著的同源性,包括与催化作用相关的独特基序,这表明聚合酶功能具有保守性。这些蛋白质是DNA损伤旁路复制蛋白的一个大型超家族的成员,包括大肠杆菌的UmuC和DinB蛋白以及酿酒酵母的Rev1和Rad30蛋白。在系统发育树中,小鼠和人类的DinB1蛋白与大肠杆菌DinB特异性地归为一组,表明这些基因起源于线粒体。人类DINB1基因定位于染色体5q13,并且广泛表达。