%0 Journal Article
%T Emerging players in the initiation of eukaryotic DNA replication
%A Zhen Shen
%A Supriya G Prasanth
%J Cell Division
%D 2012
%I BioMed Central
%R 10.1186/1747-1028-7-22
%X The proper inheritance of genomic information in eukaryotes requires both well-coordinated DNA replication in S phase and separation of duplicated chromosomes into daughter cells in mitosis [1]. Prior to S phase, pre-replication complex (pre-RC), a multi-protein complex which dictates when and where the DNA replication will initiate, is assembled [2-6]. Studies in Saccharomyces cerevisiae revealed conserved replication initiation sites (origins) that comprise a highly conserved autonomously replicating sequence (ARS) [7]. Identification of proteins bound to this sequence led to the discovery of a six-subunit complex that serves as the initiator to select replication initiation sites, and was therefore named the origin recognition complex (ORC) [8]. The assembly of pre-RC starts with ORC recognizing the replication elements and recruiting two factors, Cdc6 and Cdt1. These proteins function together to load the minichromosome maintenance proteins (MCM) onto chromatin [2-6]. This process takes place as early as the end of mitosis of the previous cell cycle [9]. In yeast, at the onset of S phase, Dbf4-dependent kinase (DDK) phosphorylation of MCMs and cyclin-dependent kinases (CDKs) phosphorylation of Sld2 and Sld3 lead to the assembly of Dpb11, GINS complex, MCM10, Cdc45, and DNA polymerase to initiation sites to form the pre-initiation complex (pre-IC), which in turn activates the MCM helicase [1-4,10,11]. In higher eukaryotes, a similar cascade has been identified, with RecQ4 and TopBP1 being orthologs for Sld2 and Dpb11 respectively [1,11]. In order to maintain the genome content, replication must occur ˇ°once and only onceˇ± during each cell cycle and re-replication must be strictly prevented. This ˇ°replication licensingˇ± mission is carried out by multiple mechanisms at the levels of the regulation of mRNA transcription, protein localization and protein stability, the presence of pre-RC inhibitors, and the alteration of local chromatin architecture [3,4,6,12-14].Sinc
%K ORC
%K ORCA/LRWD1
%K Cdt1
%K Geminin
%K MCM
%K Pre-RC
%K Pre-IC
%K RPC
%K Non-coding RNA
%K DNA replication
%U http://www.celldiv.com/content/7/1/22