Lavery P E, Kowalczykowski S C
Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611.
J Biol Chem. 1992 Oct 15;267(29):20648-58.
The recA730 mutation results in constitutive SOS and prophage induction. We examined biochemical properties of recA730 protein in an effort to explain the constitutive activity observed in recA730 strains. We find that recA730 protein is more proficient than the wild-type recA protein in the competition with single-stranded DNA binding protein (SSB protein) for single-stranded DNA (ssDNA) binding sites. Because an increased aptitude in the competition with SSB protein has been previously reported for recA441 protein and recA803 protein, we directly compared their in vitro activities with those of recA730 protein. At low magnesium ion concentration, both ATP hydrolysis and lexA protein cleavage experiments demonstrate that these recA proteins displace SSB protein from ssDNA in a manner consistent with their in vivo repressor cleavage activity, i.e. recA730 protein > recA441 protein > recA803 protein > recAwt protein. Additionally, a correlation exists between the proficiency of the recA proteins in SSB protein displacement and their rate of association with ssDNA. We propose that an increased rate of association with ssDNA allows recA730 protein to displace SSB protein from the ssDNA that occurs naturally in Escherichia coli and thereby to become activated for the repressor cleavage that leads to SOS induction. RecA441 protein is similarly activated for repressor cleavage; however, in this case, significant SSB protein displacement occurs only at elevated temperature. At physiological magnesium ion concentration, we argue that recA803 protein and wild-type recA protein do not displace sufficient SSB protein from ssDNA to constitutively induce the SOS response.
recA730突变导致组成型SOS反应和原噬菌体诱导。我们研究了recA730蛋白的生化特性,以解释在recA730菌株中观察到的组成型活性。我们发现,在与单链DNA结合蛋白(SSB蛋白)竞争单链DNA(ssDNA)结合位点时,recA730蛋白比野生型recA蛋白更具优势。因为之前已报道recA441蛋白和recA803蛋白在与SSB蛋白竞争方面能力增强,所以我们直接将它们与recA730蛋白的体外活性进行了比较。在低镁离子浓度下,ATP水解和LexA蛋白切割实验均表明,这些recA蛋白从ssDNA上取代SSB蛋白的方式与其体内阻遏物切割活性一致,即recA730蛋白>recA441蛋白>recA803蛋白>野生型recA蛋白。此外,recA蛋白在取代SSB蛋白方面的能力与其与ssDNA的结合速率之间存在相关性。我们提出,与ssDNA结合速率的增加使recA730蛋白能够从大肠杆菌中天然存在的ssDNA上取代SSB蛋白,从而被激活进行导致SOS诱导的阻遏物切割。RecA441蛋白同样被激活进行阻遏物切割;然而,在这种情况下,只有在升高温度时才会发生显著的SSB蛋白取代。在生理镁离子浓度下,我们认为recA803蛋白和野生型recA蛋白不能从ssDNA上取代足够的SSB蛋白来组成型诱导SOS反应。