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Mechanism of eukaryotic origin unwinding is a dual helicase DNA shearing process.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 12/26/2023, Vol. 120 Issue 52, p1-8. 15p. - Publication Year :
- 2023
-
Abstract
- DNA replication in all cells begins with the melting of base pairs at the duplex origin to allow access to single-stranded DNA templates which are replicated by DNA polymerases. In bacteria, origin DNA is presumed to be melted by accessory proteins that allow loading of two ring-shaped replicative helicases around single-strand DNA (ssDNA) for bidirectional unwinding and DNA replication. In eukaryotes, by contrast, two replicative CMG (Cdc45-Mcm2-7-GINS) helicases are initially loaded head to head around origin double-strand DNA (dsDNA), and there does not appear to be a separate origin unwinding factor. This led us to investigate whether head-to-head CMGs use their adenosine triphosphate (ATP)-driven motors to initiate duplex DNA unwinding at the origin. Here, we show that CMG tracks on one strand of the duplex while surrounding it, and this feature allows two head-to-head CMGs to unwind dsDNA by using their respective motors to pull on opposite strands of the duplex. We further show that while CMG is capable of limited duplex unwinding on its own, the extent of unwinding is greatly and rapidly stimulated by addition of the multifunctional CMG-binding protein Mcm10 that is critical for productive initiation of DNA replication in vivo. On the basis of these findings, we propose that Mcm10 is a processivity or positioning factor that helps translate the work performed by the dual CMG motors at the origin into productive unwinding that facilitates bidirectional DNA replication. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DNA helicases
*DNA denaturation
*SINGLE-stranded DNA
*BASE pairs
*DNA replication
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 120
- Issue :
- 52
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 174573342
- Full Text :
- https://doi.org/10.1073/pnas.2316466120