The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding.
The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding.
复制标题
细菌 DnaA-trio 复制起点元件指定单链 DNA 起始子结合。
DOI：
10.1038/nature17962
复制
发表时间：
2016-06-16
期刊：
影响因子：
64.8
通讯作者：
Murray H
中科院分区：
文献类型：
--
作者：
Richardson TT;Harran O;Murray H
DNA复制受到严格控制，以确保遗传信息的准确继承。在所有生物体中，具有AAA+（与各种细胞活性相关的ATP酶）结构域的起始蛋白结合复制起点以许可新一轮的DNA合成。在细菌中，主起始蛋白DnaA是高度保守的，具有两种关键的DNA结合活性。DnaA单体通过结合双链DNA序列（DnaA盒）识别复制起点（oriC）;随后，DnaA细丝通过接合和拉伸单个DNA链组装并促进双链体解旋。虽然DnaA对双链体DnaA盒的特异性已经被认识了三十多年，但单链DNA结合的序列特异性仍然未知。在这里，我们确定了一个新的不可或缺的细菌复制起始元件组成的重复3聚体的基序，我们长期的DNA三重奏。我们表明，DnaA-三重奏的功能是稳定DnaA丝在一个单一的DNA链，从而提供必要的精度，这种结合机制。生物信息学分析在整个细菌王国的复制起点中检测到DnaA-trios，表明该元件包含核心oriC结构的一部分。新的DnaA-trio的发现和表征扩展了我们对细菌DNA复制起始的基本理解，并且由于AAA+起始蛋白的保守结构，这些发现提高了高等生物复制起点内特异性识别基序的可能性。
DNA replication is tightly controlled to ensure accurate inheritance of genetic information. In all organisms initiator proteins possessing AAA+ (ATPases associated with various cellular activities) domains bind replication origins to license new rounds of DNA synthesis. In bacteria the master initiator protein, DnaA, is highly conserved and has two crucial DNA binding activities. DnaA monomers recognise the replication origin (oriC) by binding double-stranded DNA sequences (DnaA-boxes); subsequently, DnaA filaments assemble and promote duplex unwinding by engaging and stretching a single DNA strand. While the specificity for duplex DnaA-boxes by DnaA has been appreciated for over thirty years, the sequence specificity for single-strand DNA binding remained unknown. Here we identify a new indispensable bacterial replication origin element composed of a repeating 3-mer motif that we term the DnaA-trio. We show that the function of the DnaA-trio is to stabilise DnaA filaments on a single DNA strand, thus providing essential precision to this binding mechanism. Bioinformatic analysis detects DnaA-trios in replication origins throughout the bacterial kingdom, indicating that this element comprises part of the core oriC structure. The discovery and characterisation of the novel DnaA-trio extends our fundamental understanding of bacterial DNA replication initiation, and because of the conserved structure of AAA+ initiator proteins these findings raise the possibility of specific recognition motifs within replication origins of higher organisms.