Structure of the origin recognition complex bound to DNA replication origin
Structure of the origin recognition complex bound to DNA replication origin
复制标题
与 DNA 复制起点结合的起点识别复合物的结构
DOI：
10.1038/s41586-018-0293-x
复制
发表时间：
2018-07-12
期刊：
影响因子：
64.8
通讯作者：
Tye, Bik-Kwoon
中科院分区：
文献类型：
--
作者：
Li, Ningning;Lam, Wai Hei;Tye, Bik-Kwoon
在真核生物中，六亚基起源识别复合体（ORC）与DNA结合以标记开始复制的位置。在这里，我们报道了糖酵母菌cerevisiaeORC的3 Å低温电镜结构，该结构与包含ARS共识序列（ACS）和B1元件的72碱基对起源DNA序列结合。ORC通过与磷酸主链和碱基的广泛相互作用包围DNA，并在ACS和B1位点弯曲DNA。在ACS中胸腺嘧啶残基的特异性识别是由位于次要凹槽的Orc1的保守碱性氨基酸基序和位于主要凹槽的Orc4的物种特异性螺旋插入基序进行的。此外，类似的插入也分别由Orc2和Orc5的基本补丁基序嵌入到B1位点的主要和次要凹槽中，以接触碱基和弯曲DNA。这项工作确定了ORC在调节DNA结构以促进起源选择和解旋酶装载真核生物中的保守作用。
The six-subunit origin recognition complex (ORC) binds to DNA to mark the site for the initiation of replication in eukaryotes. Here we report a 3 Å cryo-electron microscopy structure of theSaccharomyces cerevisiaeORC bound to a 72-base-pair origin DNA sequence that contains the ARS consensus sequence (ACS) and the B1 element. The ORC encircles DNA through extensive interactions with both phosphate backbone and bases, and bends DNA at the ACS and B1 sites. Specific recognition of thymine residues in the ACS is carried out by a conserved basic amino acid motif of Orc1 in the minor groove, and by a species-specific helical insertion motif of Orc4 in the major groove. Moreover, similar insertions into major and minor grooves are also embedded in the B1 site by basic patch motifs from Orc2 and Orc5, respectively, to contact bases and to bend DNA. This work pinpoints a conserved role of ORC in modulating DNA structure to facilitate origin selection and helicase loading in eukaryotes.