Evolution of Origin Sequence and Recognition for Licensing of Eukaryotic DNA Replication

Bauer, Jack, Zali, Narges, Chouhan, Om Prakash, Demerdash, Osama El, Loell, Kaiser, Kinney, Justin Block, Joshua-Tor, Leemor W, Stillman, Bruce (March 2026) Evolution of Origin Sequence and Recognition for Licensing of Eukaryotic DNA Replication. bioRxiv. ISSN 2692-8205 (Submitted)

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Abstract

The large size of eukaryotic chromosomes necessitates that the initiation of DNA replication occurs at numerous origins of DNA replication. In S. cerevisiae, origins are highly DNA sequence-specific and are recognized by the Origin Recognition Complex (ORC). In contrast, most eukaryotes have lost features in ORC subunits that contribute to DNA sequence-specific recognition, raising the question of how origins are identified. An analysis of origins in the genome of the distantly related budding yeast Yarrowia lipolytica identified considerable variability in origin sequence and structure. High-resolution structures demonstrate that Y. lipolytica origins are recognized by a combination of ORC and Cdc6 in a manner different from S. cerevisiae. The structure of Yarrowia ORC-Cdc6 bound to different origins shows considerable plasticity in protein-DNA interactions. We compare these yeast structures to the structure of human ORC-CDC6 bound to DNA. These studies reveal information on the evolution of origins and origin recognition.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
CSHL labs > Kinney lab
CSHL labs > Stillman lab
CSHL Post Doctoral Fellows
SWORD Depositor: CSHL Elements
Highlight: Stillman, Bruce W.
Depositing User: CSHL Elements
Date: 10 March 2026
Date Deposited: 24 Mar 2026 18:14
Last Modified: 24 Mar 2026 18:14
Related URLs:
URI: https://repository.cshl.edu/id/eprint/42108

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