Umezu K, Kolodner R D
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
J Biol Chem. 1994 Nov 25;269(47):30005-13.
RecA promotes homologous pairing of single-stranded DNA (ssDNA) with double-stranded DNA (dsDNA). This reaction occurs inefficiently if the ssDNA substrate is preincubated with Escherichia coli ssDNA-binding protein (SSB). However, RecO and RecR can act together as accessory factors for RecA to overcome this inhibition by SSB (Umezu, K., Chi, N.-W., and Kolodner, R. D. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 3875-3879). To elucidate the mechanism that underlies this process, we examined protein-protein interactions between RecA, RecF, RecO, RecR, and SSB, and characterized the structure and activity of the ssDNA complexes formed with different combinations of these proteins. We obtained the following results. (i) RecO physically interacts with both RecR and SSB. The interaction between RecO and SSB is stronger than the RecO-RecR interaction. (ii) RecO and RecR do not remove SSB from SSB.ssDNA complexes, but instead bind to these complexes. The resulting RecO.RecR.SSB.ssDNA complexes were more active in RecA-mediated joint molecule formation than were SSB.ssDNA complexes. (iii) RecA can nucleate on the RecO.RecR.SSB.ssDNA complexes more efficiently than on SSB.ssDNA complexes. (iv) When RecA presynaptic filaments were formed in the presence of SSB, RecO, and RecR, the protein-DNA complexes obtained contained 70% of the amount of RecA required to saturate ssDNA. These complexes, however, can mediate joint molecule formation and strand exchange as efficiently as presynaptic filaments which are fully saturated with RecA. Based on these results, we propose dual roles for RecO and RecR in joint molecule formation. First, RecO and RecR bind to SSB.ssDNA complexes and modify their structure to allow RecA to nucleate on them efficiently. Second, RecO and RecR are retained in RecA presynaptic filaments and play a role in the subsequent homologous pairing process promoted by RecA.
RecA促进单链DNA(ssDNA)与双链DNA(dsDNA)的同源配对。如果ssDNA底物与大肠杆菌单链DNA结合蛋白(SSB)预孵育,此反应效率低下。然而,RecO和RecR可作为RecA的辅助因子共同作用,以克服SSB的这种抑制作用(Umezu, K., Chi, N.-W., and Kolodner, R. D. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 3875 - 3879)。为阐明这一过程的潜在机制,我们研究了RecA、RecF、RecO、RecR和SSB之间的蛋白质 - 蛋白质相互作用,并对由这些蛋白质的不同组合形成的ssDNA复合物的结构和活性进行了表征。我们获得了以下结果。(i)RecO与RecR和SSB均发生物理相互作用。RecO与SSB之间的相互作用强于RecO - RecR相互作用。(ii)RecO和RecR不会从SSB.ssDNA复合物中去除SSB,而是与之结合。由此产生的RecO.RecR.SSB.ssDNA复合物在RecA介导的联合分子形成中比SSB.ssDNA复合物更具活性。(iii)RecA在RecO.RecR.SSB.ssDNA复合物上成核比在SSB.ssDNA复合物上更有效。(iv)当在SSB、RecO和RecR存在的情况下形成RecA突触前细丝时,所获得的蛋白质 - DNA复合物所含RecA的量为使ssDNA饱和所需量的70%。然而,这些复合物介导联合分子形成和链交换的效率与被RecA完全饱和的突触前细丝相同。基于这些结果,我们提出RecO和RecR在联合分子形成中具有双重作用。首先,RecO和RecR与SSB.ssDNA复合物结合并改变其结构,以使RecA能够在其上有效成核。其次,RecO和RecR保留在RecA突触前细丝中,并在随后由RecA促进的同源配对过程中发挥作用。