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Early Events in DNA Replication
Author(s) -
Diffley John F.X.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.218.1
Subject(s) - genome , origin recognition complex , dna replication , random hexamer , pre replication complex , biology , microbiology and biotechnology , origin of replication , mitosis , cell cycle , cyclin , dna , eukaryotic dna replication , minichromosome maintenance , dna re replication , control of chromosome duplication , computational biology , genetics , cell , gene
The eukaryotic cell cycle coordinates the accurate duplication and segregation of the genome during proliferation. The large genomes of eukaryotic cells are replicated from multiple replication origins during S phase. These origins are not activated synchronously at the beginning of S phase, but instead fire throughout S phase according to a pre‐determined, cell type specific program. Only after the entire genome is completely replicated do cells proceed into mitosis. Ensuring that each origin is efficiently activated once and only once during each S phase is crucial for maintaining the integrity of the genome. This is achieved by a two‐step mechanism. The first step, known as licensing, involves the loading of the Mcm2–7 proteins into pre‐replicative complexes (pre‐RCs) at origins. We have recently reconstituted this reaction with purified proteins (Remus et al. Cell 2009 139: 719–30). In this reaction, Mcm2–7 are loaded as a head‐to‐head double hexamer around double stranded DNA. Mcm2–7 loading requires the Origin Recognition Complex (ORC) as well as Cdc6 and Cdt1. I will describe recent experiments showing that individual Mcm subunits play distinct roles during pre‐RC assembly by interacting with different assembly factors. I will also show that the role of cyclin dependent kinases in promoting initiation has been conserved, at least in part, between yeast and humans.