Mechanisms of replication origin licensing: a structural perspective

https://doi.org/10.1016/j.sbi.2019.08.007Get rights and content
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Highlights

  • Advances in structural biology and the development of single-molecule assays have illuminated DNA replication initiation events.

  • Cryo-EM studies of replication origin licensing intermediates have defined structural mechanisms of Mcm2-7 loading.

  • ATP binding and hydrolysis by initiation factors control multiple steps during origin licensing.

The duplication of chromosomal DNA is a key cell cycle event that involves the controlled, bidirectional assembly of the replicative machinery. In a tightly regulated, multi-step reaction, replicative helicases and other components of the DNA synthesis apparatus are recruited to replication start sites. Although the molecular approaches for assembling this machinery vary between the different domains of life, a common theme revolves around the use of ATP-dependent initiation factors to recognize and remodel origins and to load replicative helicases in a bidirectional manner onto DNA. This review summarizes recent advances in understanding the mechanisms of replication initiation in eukaryotes, focusing on how the replicative helicase is loaded in this system.

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Affiliation from 01/2020: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States.