Abstract
Faithful duplication of the genome in eukaryotes requires ordered assembly of a multi-protein complex called the pre-replicative complex (pre-RC) prior to S phase; transition to the pre-initiation complex (pre-IC) at the beginning of DNA replication; coordinated progression of the replisome during S phase; and well-controlled regulation of replication licensing to prevent re-replication. These events are achieved by the formation of distinct protein complexes that form in a cell cycle-dependent manner. Several components of the pre-RC and pre-IC are highly conserved across all examined eukaryotic species. Many of these proteins, in addition to their bona fide roles in DNA replication are also required for other cell cycle events including heterochromatin organization, chromosome segregation and centrosome biology. As the complexity of the genome increases dramatically from yeast to human, additional proteins have been identified in higher eukaryotes that dictate replication initiation, progression and licensing. In this review, we discuss the newly discovered components and their roles in cell cycle progression.
Highlights
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]
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 named the origin recognition complex (ORC) [8]
Concluding remarks Recently, several novel members have joined the family of pre-replication complex (pre-RC) (Figure 1) and preinitiation complex (pre-IC) (Figure 2), mostly discovered from proteomic screens/analyses and bioinformatic predictions; at the same time, many classic factors, including HBO1, 14-3-3, HOX, MCM10, FACT, Ctf4, and Y RNAs, were merited with additional roles in replication
Summary
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]. MCM10 binds to origins in a TopBP1 dependent manner [108] and associates with replication initiation sites before Cdc, promoting Cdc chromatin association [109,110,111], as well as after Cdc along with DNA polymerase α [103,112] This pre- and post- Cdc recruitment of MCM10 is intriguing, indicating its complicated but yet uncovered function with CMG. In Schizosaccharomyces pombe, Mrc regulates early-firing origins, independent of its checkpoint function [166] Another example comes from Xenopus Dna2 [167,168], which co-localizes with RPA during replication and interacts with Ctf4/And-1 and MCM10.
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