Mechanisms for licensing origins of DNA replication in eukaryotic cells

Bruce Stillman; John F X Diffley; Janet H Iwasa

doi:10.1038/s41594-025-01587-5

Mechanisms for licensing origins of DNA replication in eukaryotic cells

Nat Struct Mol Biol. 2025 Jun 30. doi: 10.1038/s41594-025-01587-5. Online ahead of print.

Authors

Bruce Stillman¹, John F X Diffley², Janet H Iwasa³

Affiliations

¹ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA. stillman@cshl.edu.
² Chromosome Replication Laboratory, The Francis Crick Institute, London, UK.
³ Department of Biochemistry, University of Utah, Salt Lake City, UT, USA.

PMID: 40588663
DOI: 10.1038/s41594-025-01587-5

Abstract

The initiation of DNA replication in eukaryotic cells begins with the assembly of pre-replicative complexes (pre-RCs) at many sites along each chromosome during the G1 phase of the cell cycle. Pre-RCs license each chromosome for duplication during S phase and mark the origins of DNA replication. In this Review, we discuss and contextualize recent findings identifying the mechanisms of origin recognition and pre-RC assembly mediated by the origin recognition complex (ORC), Cdc6 and the Mcm2-Mcm7 (Mcm2-7) hexamer bound to Cdt1. We also present comprehensive videos that demonstrate the multiple mechanisms for pre-RC assembly and compare the structures of the complexes involved in human and Saccharomyces cerevisiae cells.

Publication types

Review