Format

Send to

Choose Destination
See comment in PubMed Commons below
Cold Spring Harb Symp Quant Biol. 2010;75:135-42. doi: 10.1101/sqb.2010.75.062. Epub 2011 Apr 18.

The many faces of redundancy in DNA replication control.

Author information

  • 1Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom. John.Diffley@cancer.org.uk

Abstract

The large genomes of eukaryotic cells are replicated from multiple replication origins during S phase of the cell cycle. These origins are not activated synchronously at the beginning of S phase but, instead, fire throughout S phase according to a predetermined, cell-type-specific program. 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, licensing, involves the loading of the Mcm2-7 proteins into pre-replicative complexes (pre-RCs) at origins by ORC, Cdc6, and Cdt1. Pre-RCs can only assemble at origins during G(1) phase, when cyclin-dependent kinase (CDK) activity is low because CDKs inhibit each pre-RC component individually. CDKs trigger initiation by phosphorylating two essential proteins, Sld2 and Sld3. A second protein kinase, Cdc7, along with its regulatory subunit, Dbf4, is also required for initiation. In response to DNA damage, origin firing is inhibited by a third protein kinase, Rad53, which phosphorylates and inhibits Sld3 and Dbf4. In this chapter, I describe these regulatory mechanisms in detail and explore the role of redundancy in the regulation of DNA replication, focusing on the budding yeast, Saccharomyces cerevisiae.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk