Boudsocq F, Campbell M, Devoret R, Bailone A
Groupe d'Etude Mutagenèse et Cancérogenése, Institut Curie, Centre Universitaire, Orsay, France.
J Mol Biol. 1997 Jul 11;270(2):201-11. doi: 10.1006/jmbi.1997.1098.
The UmuD'C complex and RecA protein are two essential components in mutagenic repair of gaps produced by the replication of damaged DNA. In this process, the UmuD'C complex might help DNA polymerase to synthesize DNA across a lesion. Besides, a RecA polymer wrapping around single-stranded DNA could function as a directional chaperone to target the UmuD'C complex at the lesion. It was shown in our laboratory that the UmuD'C complex prevents homologous recombination and recombinational repair when expressed at elevated levels. To find out whether the UmuD'C complex inhibits recombination by interfering directly with RecA, we measured the kinetics of inhibition of Hfr x F- recombination in F- recipients in which either RecA or UmuD'C were made to vary. The cell concentrations of RecA and UmuD'C proteins were adjusted by having the recA and the umuD'C genes regulated by the arabinose P(BAD) promoter. In the absence of the UmuD'C complex, recombination was a function of RecA concentration and then reached a plateau when the RecA concentration was above 9000 monomers/cell. At a fixed RecA concentration, the yield of Hfr x F- recombinants decreased as a function of the UmuD'C cell concentration. At a given UmuD'C/RecA ratio, recombination inhibition by UmuD'C was reversed by increasing the RecA cell concentration. RecA1730, a mutant protein impaired in the chaperone activity, was insensitive to UmuD'C inhibition. We propose a model accounting for the RecA chaperone function in SOS mutagenesis and for the UmuD'C inhibitory effect on homologous recombination. We suggest that the UmuD'C complex is placed at the tip of a RecA polymer as a result of a treadmilling process. This would position the UmuD'C complex right at a lesion while the capping by UmuD'C would destabilize a RecA polymer and thereby abort the recombination process.
UmuD'C复合物和RecA蛋白是受损DNA复制产生缺口的诱变修复中的两个关键成分。在此过程中,UmuD'C复合物可能帮助DNA聚合酶跨越损伤部位合成DNA。此外,围绕单链DNA的RecA聚合物可作为定向伴侣,将UmuD'C复合物靶向损伤部位。我们实验室的研究表明,当UmuD'C复合物高水平表达时,它会阻止同源重组和重组修复。为了确定UmuD'C复合物是否通过直接干扰RecA来抑制重组,我们在F-受体中测量了Hfr x F-重组抑制的动力学,其中RecA或UmuD'C的表达量发生变化。通过让recA和umuD'C基因受阿拉伯糖P(BAD)启动子调控,来调节RecA和UmuD'C蛋白的细胞浓度。在没有UmuD'C复合物的情况下,重组是RecA浓度的函数,当RecA浓度高于9000个单体/细胞时达到平台期。在固定的RecA浓度下,Hfr x F-重组体的产量随着UmuD'C细胞浓度的增加而降低。在给定的UmuD'C/RecA比例下,增加RecA细胞浓度可逆转UmuD'C对重组的抑制作用。RecA1730是一种伴侣活性受损的突变蛋白,对UmuD'C的抑制不敏感。我们提出了一个模型,解释了RecA伴侣功能在SOS诱变中的作用以及UmuD'C对同源重组的抑制作用。我们认为,由于踏车行为,UmuD'C复合物位于RecA聚合物的末端。这将使UmuD'C复合物正好位于损伤部位,而UmuD'C的封端作用会使RecA聚合物不稳定,从而中止重组过程。