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Updated: Jul 2, 2025
11:19
Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 7, 2010
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TopBP1 utilises a bipartite GINS binding mode to support genome replication.
Matthew Day1,2, Bilal Tetik3, Milena Parlak3
1School of Biological and Behavioural Sciences, Blizard Institute, Queen Mary University of London, London, E1 2AT, UK. matthew.day@qmul.ac.uk.
Nature Communications
|February 27, 2024
Summary
The GINS complex and TopBP1 protein interact via two distinct surfaces, crucial for DNA replication origin firing. This interaction is essential for faithful genetic inheritance and involves coordination with DNA polymerase epsilon.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- Replication origin firing requires Mcm2-7 helicase activation by GINS and Cdc45.
- Faithful genetic inheritance depends on accurate DNA replication.
Purpose of the Study:
- To elucidate the interaction mechanism between the helicase activator GINS and TopBP1.
- To understand the role of this interaction in DNA replication origin firing.
Main Methods:
- Biochemical and structural studies.
- Mutation analysis in Xenopus egg extracts.
- Analysis of protein-protein interactions.
Main Results:
- GINS interacts with TopBP1 through two separate binding surfaces on TopBP1 (GINI region and BRCT4) and the GINS subunit Psf1.
- Either binding surface alone supports the TopBP1-GINS interaction, with reduced affinity.
- Both surfaces are sufficient for replication origin firing in Xenopus egg extracts and essential when the other is absent.
- TopBP1-GINS interaction is sterically incompatible with simultaneous DNA polymerase epsilon binding to GINS.
Conclusions:
- A model for TopBP1-GINS interaction is proposed, enhancing understanding of the metazoan pre-loading complex.
- The findings predict the coordinated regulation of DNA polymerase epsilon arrival, TopBP1 ejection, and GINS integration during origin firing.
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