G-quadruplex-induced instability during leading-strand replication
G-quadruplex-induced instability during leading-strand replication
复制标题
DOI：
10.1038/emboj.2011.316
复制
发表时间：
2011-10-05
期刊：
影响因子：
11.4
通讯作者：
Nicolas, Alain
中科院分区：
文献类型：
--
作者：
Lopes, Judith;Piazza, Aurele;Nicolas, Alain
G-四链体是四链核酸结构，其生物学功能仍然知之甚少。在酵母S.酿酒酵母，我们报告的G-四链体的形式，如果不适当的处理，复制提出了具体的挑战。我们表明，G-四链体倾向CEB 1串联阵列是容忍的插入附近的ARS 305复制起点在野生型细胞，但非常频繁的治疗后，与有效的Phen-DC 3 G-四链体配体，或在没有G-四链体解旋Pif 1解旋酶，只有当G-丰富的链是模板的前导链复制不稳定。方向依赖性不稳定性与二维（2D）凝胶检测复制过程中Rad 51-Rad 52依赖性X形中间体的形成有关，并依赖于CEB 1中完整G-四链体基序的存在和ARS 305的活性。在复制过程中的G-四链体倾向序列的不对称行为有其进化动力学的基因组内，包括维护G-丰富的端粒的影响。The EMBO Journal（2011）30，4033-4046. doi：10.1038/daj.2011.316; 2011年8月26日在线发布
G-quadruplexes are four-stranded nucleic acid structures whose biological functions remain poorly understood. In the yeast S. cerevisiae, we report that G-quadruplexes form and, if not properly processed, pose a specific challenge to replication. We show that the G-quadruplex-prone CEB1 tandem array is tolerated when inserted near ARS305 replication origin in wild-type cells but is very frequently destabilized upon treatment with the potent Phen-DC3 G-quadruplex ligand, or in the absence of the G-quadruplex-unwinding Pif1 helicase, only when the G-rich strand is the template of leading-strand replication. The orientation-dependent instability is associated with the formation of Rad51-Rad52-dependent X-shaped intermediates during replication detected by two-dimensional (2D) gels, and relies on the presence of intact G-quadruplex motifs in CEB1 and on the activity of ARS305. The asymmetrical behaviour of G-quadruplex prone sequences during replication has implications for their evolutionary dynamics within genomes, including the maintenance of G-rich telomeres. The EMBO Journal (2011) 30, 4033-4046. doi:10.1038/emboj.2011.316; Published online 26 August 2011