Prabhu Vidya P, Simons Amanda M, Iwasaki Hiroshi, Gai Dahai, Simmons Daniel T, Chen Junghuei
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA.
J Mol Biol. 2002 Mar 8;316(5):1023-32. doi: 10.1006/jmbi.2001.5408.
The Holliday junction is the central intermediate in homologous recombination. Branch migration of this four-stranded DNA structure is a key step in genetic recombination that affects the extent of genetic information exchanged between two parental DNA molecules. Here, we have constructed synthetic Holliday junctions to test the effects of p53 on both spontaneous and RuvAB promoted branch migration as well as the effect on resolution of the junction by RuvC. We demonstrate that p53 blocks branch migration, and that cleavage of the Holliday junction by RuvC is modulated by p53. These findings suggest that p53 can block branch migration promoted by proteins such as RuvAB and modulate the cleavage by Holliday junction resolution proteins such as RuvC. These results suggest that p53 could have similar effects on eukaryotic homologues of RuvABC and thus have a direct role in recombinational DNA repair.
霍利迪连接体是同源重组的核心中间体。这种四链DNA结构的分支迁移是基因重组中的关键步骤,它影响两个亲本DNA分子之间交换的遗传信息的范围。在这里,我们构建了合成霍利迪连接体,以测试p53对自发和RuvAB促进的分支迁移的影响,以及对RuvC介导的连接体解离的影响。我们证明p53会阻断分支迁移,并且RuvC对霍利迪连接体的切割受到p53的调节。这些发现表明,p53可以阻断由RuvAB等蛋白质促进的分支迁移,并调节由RuvC等霍利迪连接体解离蛋白介导的切割。这些结果表明,p53可能对RuvABC的真核同源物有类似的影响,因此在重组DNA修复中具有直接作用。