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Chromatin's Influence on Pre-Replication Complex Assembly and Function
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DOI：10.3390/biology13030152.png)
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Simple Summary Genome duplication and the faithful segregation of chromosomes to daughter cells are crucial for the maintenance of genome stability. Replication initiators play a crucial role in ensuring that DNA replication occurs only once per cell division cycle. This review summarizes when, where, and how replication initiates in human cells.Abstract In all eukaryotes, the initiation of DNA replication requires a stepwise assembly of factors onto the origins of DNA replication. This is pioneered by the Origin Recognition Complex, which recruits Cdc6. Together, they bring Cdt1, which shepherds MCM2-7 to form the OCCM complex. Sequentially, a second Cdt1-bound hexamer of MCM2-7 is recruited by ORC-Cdc6 to form an MCM double hexamer, which forms a part of the pre-RC. Although the mechanism of ORC binding to DNA varies across eukaryotes, how ORC is recruited to replication origins in human cells remains an area of intense investigation. This review discusses how the chromatin environment influences pre-RC assembly, function, and, eventually, origin activity.
Keyword:
DNA replication
chromatin
ORC
pre-replication complex (pre-RC)
epigenetics
polycomb (Pc)
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